Jochanan E. Naschitz

Rheumatic syndromes: Clues to occult neoplasia

Rheumatic disorders associated with cancer include a variety of conditions, most of which have no features distinguishing them from idiopathic rheumatic disorders. It is generally held that an extensive search for occult malignancy in most rheumatic syndromes is not recommended unless the case is accompanied by specific findings suggestive of malignancy. Within the past year information has accumulated on the role of long-standing rheumatic disorders as premalignant conditions and the role of autoantibodies as screening tests for occult cancer. The present article discusses cancer-associated rheumatic syndromes, calls attention to aspects that may suggest the presence of a hidden cancer, and examines the role of laboratory tests as clues of a possible neoplastic etiology of those syndromes.

Orthostatic hypotension : framework of the syndrome

According to the 1996 consensus definition, orthostatic hypotension (OH) is diagnosed when a fall in systolic blood pressure of at least 20 mm Hg and/or diastolic blood pressure of at least 10 mm Hg within 3 min of standing is recorded. The elements of orthostatic blood pressure drop that are relevant to the definition of OH include magnitude of the drop, time to reach the blood pressure difference defined as OH, and reproducibility of the orthostatic blood pressure drop. In each of these elements, there exist issues that argue for modification of the presently accepted criteria of OH. Additional questions need to be addressed. Should one standard orthostatic test be applied to different patient populations or should tests be tailored to the patients’ clinical circumstances? Are different OH thresholds relevant to various clinical settings, aetiologies of OH and comorbidity? Which test has the best predictive power of morbidity and mortality?

Pulse transit time by R-wave-gated infrared photoplethysmography : Review of the literature and personal experience

Objective. Pulse transit time (PTT) is the time it takes a pulse wave to travel between two arterial sites. A relatively short PTT is observed with high blood pressure (BP), aging, arteriosclerosis and diabetes mellitus. Most methods used for measuring the PTT are cumbersome and expensive. In contrast, the interval between the peak of the R-wave on the electrocardiogram and the onset of the corresponding pulse in the finger pad measured by photoplethysmography can be easily measured. We review herein the literature and impart the experience at our institution on clinical applications of R-wave-gated photoplethysmography (RWPP) as measurement of PTT. Methods. The MEDLINE data base on clinical applications of RWPP was reviewed. In addition, studies performed in the author’s institution are presented. Results. When used as a surrogate for beat-to-beat BP monitoring, RWPP did not meet the level of accuracy required for medical practice (two studies). RWPP produced accurate and reproducible signals when utilized as a surrogate for intra-thoracic pressure changes in obstructive sleep apnea, as well as BP arousals which accompany central sleep apnea (five studies). In estimation of arterial stiffness, RWPP was unsatisfactory (one study). In assessment of cardiovascular reactivity, abnormal values of RWPP were noted in autonomic failure (one study), while disease-specific reactivity patterns were identified utilizing a method involving RWPP (two studies). Conclusions. In clinical practice, sleep-apnea may be accurately monitored by RWPP. RWPP seems to reflect autonomic influences and may be particularly well-suited for the study of vascular reactivity. Thus, further descriptions of disease-specific cardiovascular reactivity patterns may be possible with techniques based on RWPP. Other clinical uses of RWPP are investigational.

Cancer-associated rheumatic disordersclues to occult neoplasia

Interest in the rheumatologic manifestations of cancer is related in part to practical considerations, ie, earlier cancer diagnosis is possible through enhanced awareness of cancer-associated rheumatic syndromes. The spectrum of rheumatic disorders associated with cancer includes over 30 conditions, including hypertrophic osteoarthropathy, polymyalgia rheumatica, palmar fasciitis with polyarthritis, most autoimmune connective tissue diseases, and the more recently described antiphospholipid syndrome. It is generally held that extensive search for occult malignancy in most rheumatologic disorders is not cost efficient and not recommended unless accompanied by specific findings suggestive of malignancy. The present article discusses the supplementary findings that may justify malignancy evaluation.

Acute neutrophilic myositis in sweet's syndrome: Late phase transformation into fibrosing myositis and panniculitis

Early in the course of myeloblastic leukemia a patient concurrently developed febrile neutrophilic dermatosis and sterile acute myositis. The dermatitis and myositis were unresponsive to antibiotic therapy but remitted within a few days of institution of steroid treatment. The patient died of myocardial infarction. At autopsy the dermis was normal. Previously effected muscles were scarred. The overlying fascia and subcutaneous septa were fibrotically thickened. In addition, segmental acute aortitis was detected. Acute myositis and aortitis may reflect further organ manifestations of the Sweets reactivity pattern. It is proposed that Sweets myositis and dermatitis may evolve into a fibrosing myositis and panniculitis.

Vascular Disorders Preceding Diagnosis of Cancer: Distinguishing the Causal Relationship based on Bradford-Hill Guidelines

The literature investigating the association between vascular disorders and malignant neoplasms does not comprehensively review the full spectrum of vascular disorders associated with cancer, or provide proof that cancer is an etiologic factor in the development of these disorders. This paper investigates the causal role of cancer in the pathogenesis of vascular disorders, based on the Bradford-Hill criteria of causation. The Medline database was searched for articles on vascular disorders preceding the diagnosis of cancer (VDPCD). Included in the analysis were vascular disorders caused either by direct tumoral involvement of vessels or by paraneoplastic mechanisms. Vascular disorders caused by adverse reactions to anticancer therapy were excluded from analysis. Seven categories of VDPCDs were recognized: venous thromboembolism, arterial thrombosis and embolism, nonbacterial thrombotic endocarditis, migratory superficial thrombophlebitis, vasculitis, thrombotic microangiopathy, and leukothrom bosis. To establish causality of the association between VDPCDs and malignancy, the degree of fulfillment of the Bradford-Hill criteria was assessed. A strong association was found in the literature between venous thromboembolism and cancer (OR 2.3-14.9 and SIR 1.3-4.4). Consistency and temporality of the association were confirmed in all VDPCD variants. Seven Bradford-Hill criteria were fulfilled for cancer associated with venous thromboembolism, six criteria for superficial phlebitis and cancer, and five criteria for each of the other VDPCDs. In conclusion, these data support the causal role of cancer in the pathogenesis of all seven cate gories of VDPCDs. Recognition of such a causal link between cancer and various vascular disorders may promote an earlier cancer diagnosis.

Quantitative liver-spleen scan using single photon emission computerized tomography (SPECT) for assessment of hepatic function in cirrhotic patients

BACKGROUND/AIMS Accurate quantitative determination of liver function is critical in cirrhotic patients in order to predict outcome, particularly in patients who undergo hepatic resection or non-hepatic surgery. As colloid uptake by perfused Kupffer cells is proportional to perfused hepatocyte mass, quantitative liver spleen scan may be used as an index of perfused hepatocyte mass. Thus, this study was conducted to evaluate quantitative single photon emission computerized tomography (SPECT) of Tc-99mm-phytate colloid uptake by the liver as a test for hepatic function in cirrhotic patients. METHODS Quantitative SPECT was used to measure liver volume, quantitative colloid uptake by the liver and percentage of injected dose/ml of liver tissue in cirrhotic patients (n=75), non-cirrhotic patients with chronic liver disease (n=52) and patients without liver disease (n=36). RESULTS Although liver volume was similar among the three groups, the cirrhotic patients had significantly lower total quantitative uptake and quantitative uptake/ml compared to groups 2 and 3 (P<0.001). Quantitative liver uptake in the cirrhotic patients was highly correlated with Child-Pugh score (r=-0.64, P<0.0001) and with indocyanine green retention at 15 min (r=-0.84, P<0.0001). CONCLUSIONS Quantitative SPECT of the liver may be an additional, useful, non-invasive quantitative test for assessment of hepatic function and severity of liver disease in cirrhotic patients.

Fractal analysis and recurrence quantification analysis of heart rate and pulse transit time for diagnosing chronic fatigue syndrome

Abstract. This study aimed to develop a method to distinguish between the cardiovascular reactivity in chronic fatigue syndrome (CFS) and other patient populations. Patients with CFS (n = 23), familial Mediterranean fever (n = 15), psoriatic arthritis (n = 10), generalized anxiety disorder (n = 12), neurally mediated syncope (n = 20), and healthy subjects (n = 20) were evaluated with a shortened head-up tilt test (HUTT). A 10-minute supine phase of the HUTT was followed by recording 600 cardiac cycles on tilt, i. e., 5 to 10 minutes. Beat-to-beat heart rate (HR) and pulse transit time (PTT) were acquisitioned. Data were processed by recurrence plot and fractal analysis. Fifty-two variables were calculated in each subject. On multivariate analysis, the best predictors of CFS were HR-tilt-R/L, PTT-tilt-R/L, HR-supine-DET, PTT-tilt-WAVE, and HR-tilt-SD. Based on these predictors, the ‘Fractal & Recurrence Analysis-based Score’ (FRAS) was calculated: FRAS = 76.2 + 0.04*HR-supine-DET – 12.9*HR-tilt-R/L – 0.31*HR-tilt-SD – 19.27*PTT-tilt-R/L – 9.42* PTT-tilt-WAVE. The best cut-off differentiating CFS from the control population was FRAS = + 0.22. FRAS > + 0.22 was associated with CFS (sensitivity 70 % and specificity 88 %). The cardiovascular reactivity received mathematical expression with the aid of the FRAS. The shortened HUTT was well tolerated. The FRAS provides objective criteria which could become valuable in the assessment of CFS.

Amiodarone toxicity presenting as pulmonary mass and peripheral neuropathy: the continuing diagnostic challenge

A 64 year old man receiving long term amiodarone treatment presented with dyspnea, cough, and weight loss. Radiographs and computed tomography showed a lung mass with associated multiple pulmonary nodules. Biopsies of the pulmonary mass showed foamy histiocytes without malignant cells. However, findings on FDG-PET scan were consistent with a malignant tumour. These findings on computed tomography and PET scan and the unusually late resolution of the pulmonary lesions after withdrawal of amiodarone treatment posed a challenging diagnostic problem.

Patterns of hypocapnia on tilt in patients with fibromyalgia, chronic fatigue syndrome, nonspecific dizziness, and neurally mediated syncope.

Objectives:To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF). Patients and Methods:A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation. Results:Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients. Conclusions:Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.