Nizar Elias

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.

The patient with supine hypertension and orthostatic hypotension: a clinical dilemma.

Coexistent supine hypertension and orthostatic hypotension (SH-OH) pose a particular therapeutic dilemma, as treatment of one aspect of the condition may worsen the other. Studies of SH-OH are to be found by and large on patients with autonomic nervous disorders as well as patients with chronic arterial hypertension. In medical practice, however, the aetiologies and clinical presentation of the syndrome seem to be more varied. In the most typical cases the diagnosis is straightforward and the responsible mechanism evident. In those patients with mild or non-specific symptoms, the diagnosis is more demanding and the investigation may benefit from results of the tilt test, bedside autonomic tests as well as haemodynamic assessment. Discrete patterns of SH-OH may be recognisable. This review focuses on the management of the patient with coexistent SH-OH.

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.

Colonic ulcers in a patient with hepatitis C virus-associated polyarteritis nodosa

An elderly woman presented with abdominal discomfort, pulmonary infiltrates, acute renal failure, purpura, and massive hematochezia. Numerous colonic ulcers with underlying fibrinoid necrotizing arteritis were found in the colectomy specimen. Anti-hepatitis C virus (HCV) antibodies and HCV RNA were present in the serum. The diagnosis of HCV-associated polyarteritis nodosa was clear. This clinical presentation differs from the more commonly occurring vasculitis complicating HCV infection, which is of the leukocytoclastic type, and is associated with overt liver disease and cryoglobulinemia. In our patient, results of liver tests were normal, there was no cryoglobulinemia, and the vasculitis was of the fibrinoid necrotizing arteritis type. HCV-associated polyarteritis nodosa should be considered in the differential diagnosis of necrotizing fibrinoid arteritis even in a patient with normal liver function test results and in the absence of cryoglobulinemia.

Abnormal erythrocyte rheology in patients with morbid obesity.

The objectives of this study were to investigate the rheological properties of the erythrocyte in patients with morbid obesity and to follow them up after a short-term weight loss. A fluorescent polarization method was used to assess erythrocyte membrane biorheology and to measure its fluidity. Eighteen sub jects participated in the study: 8 healthy controls and 10 patients with morbid obesity. The erythrocyte membrane fluidity was obtained in the healthy subjects and in the patients with morbid obesity prior to and after a ten-day zero-calorie diet. Fluidity was determined by steady-state fluorescence polarization after incorpo ration of the lipophilic probe 1,6-diphenyl-1,3,5 hexatriene (DPH). With this method, the anisotropy parameter at 37 ° C, which is inversely related to mem brane fluidity, was obtained. The patients with morbid obesity revealed an abnormal erythrocyte rheol ogy. They exhibited an abnormally low erythrocyte membrane fluidity as com pared with normal subjects. The anisotropy parameter at 37°C was 1.417 ± 0.093 in these obese patients compared with 1.279 ± 0.043 in normal- weight controls (p < 0.01). Upon a short-term significant weight loss from a body mass index (BMI) (weight/height2) of 39 ± 5 to 36 ± 5 kg/m2 (p < 0.05), the anisotropy parameter did not change (1.401 ±0.190). Thus, fluidity measurements permit recognition of an abnormal erythrocyte rheology in patients with morbid obesity. This abnormality may partially ex plain the excess cardiovascular and thromboembolic morbidity in morbid obe sity.

A possible analytical and clinical role of endogenous antibodies causing discrepant adrenocorticotropic hormone measurement in a case of ectopic Cushing's syndrome.

Heterophilic antibodies are well described, but poorly appreciated interferents and is often not a recognized problem affecting most immunoassays. We report a patient presented with ectopic Cushing’s syndrome (CS), but repeated plasma adrenocorticotropic hormone (ACTH) concentrations conducted by immunoassay were inappropriately within the reference range and not elevated, most probably as a result of antibody interference. A 36-year-old woman, presented with large gastric neuroendocrine carcinoma and severe ectopic CS, while repeated plasma ACTH concentrations conducted by immunoassay were inappropriately within the reference range. As we expected ACTH concentration to be higher, we performed several tests to evaluate whether there was any assay interference causing falsely lower than expected ACTH results. We measured ACTH using a different immunoassay, assayed the sample in dilution, assayed the sample after being incubated in heterophilic antibody blocking agent tube and performed recovery studies. Tests indicated the presence of interfering compounds, most probably heterophilic antibodies. When clinicians find ACTH concentrations to be lower than expected, we recommend the laboratory investigate antibody interference.

Predicting outcomes on head-up tilt based on orthostatic hypotension patterns.

Objective To assess the frequency of different orthostatic hypotension (OH) patterns in patients having supine hypertension with OH (‘SHOH’) versus patients with OH and normal supine blood pressure (‘OH alone’); and to relate OH patterns with outcomes on head-up tilt. Methods Consecutive patients with nonspecific dizziness were studied with a 10-min supine, 30-min head-up tilt test. Supine hypertension was diagnosed when supine systolic blood pressure (SBP) was at least 140 mmHg and/or supine diastolic blood pressure was at least 90 mmHg. OH was defined as SBP reduction of at least 20 mmHg within 3 min of tilt. OH patterns were identified corresponding to SBP time-curves during the initial 5 min of tilt: progressive, sustained and transient patterns. Results Among 400 patients tested, 31 had ‘SHOH’ and 39 had ‘OH alone’. Frequencies of OH patterns were similar in both groups. The progressive OH pattern predicted symptomatic hypotension, leading to early tilt termination in all ‘SHOH’ and 88% of ‘OH alone’ patients. In comparison, tilt was early terminated in 33–48% of patients with sustained OH, transient OH and without OH. Early tilt termination was unrelated to age, gender, magnitude of supine SBP, pulse pressure and nadir SBP within 5 min tilt. Conclusions Five minutes of postural challenge permitted assessing OH patterns. Outcome on protracted tilt was related to OH patterns, the worse outcome being likened to progressive OH, both in patients with ‘SHOH’ and in patients with ‘OH alone’. Future studies will show whether OH patterns may serve as guidance for blood pressure therapy in selected patients.

Q Fever Risk in Patients Treated with Chronic Antitumor Necrosis Factor-Alpha Therapy

Q fever is a zoonotic bacterial disease caused by Coxiella burnetii. Tumor necrosis factor-alpha (TNF-α) plays a pivotal role in the defense against infection with this Gram-negative coccobacillus. Theoretically, patients who are treated with anti-TNF-α medications are at risk for developing chronic Q fever. We present two patients who developed Q fever while being treated with anti-TNF-α agents and discuss the significance of timely diagnosis of C. burnetii infection in these patients.

Rapid progression to cardiac tamponade in Erdheim–Chester disease despite treatment with interferon alpha

Erdheim–Chester disease (ECD) is a rare form of non-Langerhans histiocytosis with heterogeneous clinical manifestations. The most common presentation is bone pains typically involving the long bones. Approximately 75% of the patients develop extraskeletal involvement. Cardiac involvement is seen in up to 45% of the patients, and although, pericardial involvement is the most common cardiac pathology of this rare disease, cardiac tamponade due to ECD has been very rarely reported. We describe a case of a patient found to have ECD with multi-organ involvement and small pericardial effusion, which progressed to cardiac tamponade despite treatment with interferon alpha.