Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome.

Diffuse alveolar hemorrhage (DAH) is a rare manifestation of primary antiphospholipid antibody syndrome (APS). We describe a patient with primary APS and refractory recurrent episodes of DAH. The patient was admitted 15 times due to recurrent episodes of DAH in a period of 18 months. Multiple immunosuppressive drugs did not improve his condition. Two years after his presentation, he was treated with rituximab (two doses of 1 g, 2 weeks apart). Six months later, the attacks of DAH have gradually disappeared. In a follow-up of more than 2 years after he received rituximab, the patient has had no further admissions due to DAH. Levels of antiphospholipid antibodies were measured during follow-up of 4 years. Anti-ß2 glycoprotein IgG titer decreased to normal 6 months after therapy but anticardiolipin (aCL) antibody titer increased. We conclude that rituximab caused a dramatic clinical response in this patient. Anti-ß2 glycoprotein IgG correlated better with the clinical response in this patient than aCL.

Secondary syphilis presenting as SAPHO syndrome features.

The SAPHO syndrome may evolve following low virulent infections. This report describes a patient who developed a clinical syndrome that complied with the formal diagnostic criteria of the SAPHO following an infection with syphilis. His clinical manifestations gradually resolved following antibiotic therapy. This interesting association underlines the pathogenic circumstances linking infections and various rheumatic conditions. It is less evident whether resolution of the symptoms was ascribed to the eradication of the bacteria or perhaps due to cessation of the auto-inflammatory reaction to the infection induced. In our description we suggest a correlation between infection with Treponema pallidum and the induction of SAPHO syndrome.

Physical activity protects male patients with post-traumatic stress disorder from developing severe fibromyalgia.

OBJECTIVES: Fibromyalgia syndrome (FMS) has been associated with various psychiatric and other, ill-defined disorders. We recently showed that fibromyalgia is more prevalent in men suffering from combat-related Post Traumatic Stress Disorder (PTSD). In this paper we analyze the relationship between engagement in physical activity, the psycho-metric traits of PTSD and the future development of FMS. METHODS: Fifty-five male patients, all known to have combat-related PTSD, were investigated for the presence of fibro-myalgia according to the American College of Rheumatology (ACR) criteria. Each patient completed questionnaires characterizing his quality of sleep, and the Sheehan Disability Scale measuring performance in the familial, social and vocational spheres. Additionally, each of the enrollees was interviewed by an experienced psychiatrist, who then completed a Clinician Administered PTSD Scale, a Clinical Global Impression Scale, and calculated an SF-36 score. Each patient was asked whether he exercised often, occasionally or not at all. The data was analyzed by the chi2 test and by ANOVA. RESULTS: PTSD patients who also suffered from FMS had a more severe form of disease as measured by the Clinician Administered PTSD Scale (CAPS) score, 88.2 +/- 14.0 (n = 28) compared to 97.6 +/- 13.2 of patients with PTSD and FMS (n = 27) (p = 0.013, F(d.f 2)-6.61, ANOVA test). Interestingly, engaging in physical exercise was also associated with less severe disease. When the patients were analyzed based on their tender point count (0-5, 6-10, or > 11), the number of tender points decreased with increasing physical activity (p = 0.02, chi2(d.f.-4) = 11.3). CONCLUSION: Physical exercise in male patients with combat-related PTSD provides protection from the future development of fibromyalgia. Furthermore, physical activity is related in this group of patients to a better perception of their quality of life.

Attitudes of medical practitioners towards "Do Not Resuscitate" orders.

When the desires of a patient are unknown or cannot be ascertained, cardio-pulmonary resuscitation (CPR) is the default procedure. Explicit, Do Not Resuscitate (DNR), orders are required to prevent implementation of CPR. We studied the response of general medical internists in specific clinical situations demanding consideration of DNR orders and respect for patient preferences; their current practice regarding slow codes and participation in CPR attempts considered futile provide information as to how often they discuss DNR issues with patients or families. Eighty-five internists attending the monthly meeting of the Internal Medicine Forum participated in the study. The physicians demonstrated their consent to participate by accepting a remote transmitter that elicited a response 2-3 minutes following the presentation of case vignettes or practice-related questions. The survey showed that 73% of the physicians agreed to assign a DNR order for a terminally ill patient unable to express her preferences. Only 55% agreed to do the same for a competent patient who specifically requested that CPR be withheld in the event of a cardiopulmonary arrest (p<0.05). 77% reported to have performed CPR, at least three times, in situations where they expected no benefit. 59% affirmed that their team had performed a partial CPR (slow code) at least once. Only 28% discussed the subject of DNR with patients or family more than 5 times a year. Paternalism, disregard for patients' preferences and poor communication skills influence normative behaviour in end-of-life decision-making.

Cardiac arrhythmias in systemic amyloidosis: correlation with echocardiographic abnormalities.

To determine the prevalence of cardiac arrhythmias in patients with systemic amyloidosis 24 hour electrocardiographic monitoring was performed in 27 patients with primary amyloidosis and in 6 patients with familial amyloid polyneuropathy. All patients underwent echocardiographic studies. Despite a high prevalence of conduction disturbances on standard electrocardiogram, clinically significant bradyarrhythmias were rare (one patient). Complex ventricular arrhythmias (multiform, paired or repetitive beats) occurred in 14 patients (47%) with primary amyloid and 3 patients (50%) with familial amyloid polyneuropathy. The presence of cardiac arrhythmia correlated with heart failure and, more strongly, with an abnormal echocardiogram. There were four sudden deaths, all in patients with abnormal echocardiograms and complex ventricular arrhythmias. These findings suggest that complex ventricular arrhythmia on Holter monitoring is common in cardiac amyloidosis and may be a harbinger of subsequent sudden cardiac death.

Alveolar hemorrhage in cryoglobulinemia--an indicator of poor prognosis.

OBJECTIVE: Alveolar vasculitis is an unusual event in the course of cryoglobulinemia (CG). The inflammatory process involving the alveolar capillary walls may result in severe alveolar hemorrhage and consequently lead to a grave outcome. The objective of this study was to evaluate the occurrence of this unusual finding in CG. METHODS: We reviewed the records of all patients with CG who developed acute alveolitis, registered their associated clinical and laboratory parameters and evaluated the possible impact these parameters may have on their prognosis. In addition we scanned the Medline for similar cases. RESULTS: Of the 125 patients with CG who were hospitalized in our medical center during the last 23 years, 4 (3.2%) developed alveolar hemorrhage. All patients exhibited extreme fatigue, fever with clinical and radiological evidence of alveolitis. Of the 4 new cases, 1 had type II CG and 3 had type III CG. Of our 4 patients, 3 developed concomitant acute renal failure necessitating hemodialysis. A literature survey resulted in 6 additional cases. All 10 patients experienced acute respiratory insufficiency and eight had at least one episode of hemoptysis. In the other 2 patients the bronchoalveolar lavage (BAL) fluid contained hemosiderin laden macrophages. Five of the 10 patients had concomitant hepatitis C virus (HCV) infection; 2 patients were seen prior to modern identification of the HCV; however, liver abnormalities were not described. Of the 10 patients 5 patients had type II CG and 5 others had type III. Of the 7 patients in whom outcome was available, 6 died from their illness. Acute renal failure or exacerbation of antecedent glomerular disease occurred in 8 patients. CONCLUSIONS: Alveolitis is a rare manifestation of CG, presenting as an overwhelming systemic illness and portends a poor prognosis with a high mortality rate.

Skin involvement in familial amyloidotic polyneuropathy.

A 3-mm punch biopsy of clinically normal skin was obtained from the forearm of 11 patients from five kinships with familial amyloid polyneuropathy. Seven of the 11 patients had sensory polyneuropathy in the arms as well as the legs. Abnormalities of the autonomic nervous system (nocturnal diarrhea and sphincter abnormalities) were observed in all patients. Four patients had multiple atrophic scars and poorly healed ulcers on the limb; two had petechiae after gentle stroking of the skin. Histopathology revealed amyloid deposits in all 11 skin biopsies (100%). Amyloid infiltration was noted in blood vessels, sweat glands, dermis, and arrector pili muscles. Intracutaneous neural deposits were not found. Skin biopsies from family members at risk may be an effective method of early diagnosis.

Familial amyloid polyneuropathy: a new kinship of German ancestry.

Familial amyloid polyneuropathy (FAP) is an autosomal dominant inherited disorder that primarily affects the peripheral and autonomic nervous systems and usually becomes symptomatic in the third or fourth decade. Because of the confusion with other genetically transmitted neurologic conditions, the diagnosis is often delayed until advanced stages. We describe a new German kinship with FAP in which the disorder was detected in two asymptomatic family members who were seeking genetic counseling.

Esophageal manometry in familial amyloid polyneuropathy.

The motility of the esophagus was studied by esophageal manometry in eight patients with familial amyloid polyneuropathy. All eight patients had an abnormality of the lower esophageal sphincter. Seven of eight had a borderline or decreased lower esophageal sphincter pressure and the other patient had a non-relaxing lower esophageal sphincter pressure. Six of eight patients had abnormalities of the body of the esophagus consisting of either simultaneous or decreased amplitude of contractions involving the smooth or striated muscle or both. In addition, seven of eight patients had diarrhea and six of these seven patients had evidence for steatorrhea. The manometric abnormalities observed were consistent with deposition of amyloid in smooth and striated muscle as well as in the enteric nervous system. Esophageal manometry appears to be a sensitive technique to determine if the gastrointestinal tract is involved in familial amyloid polyneuropathy.

Esophageal manometry in systemic amyloidosis. A study of 30 patients.

The motility of the esophagus was studied by esophageal manometry in 24 patients with primary amyloidosis and six with secondary amyloidosis. Resting lower esophageal sphincter pressure was decreased in 12 patients with primary amyloidosis and two with secondary amyloidosis; 12 of these 14 patients complained of heartburn. Abnormalities in the motility of the body of the esophagus were found in nine patients with primary amyloidosis and one with secondary amyloidosis. No abnormality of the upper esophageal sphincter was demonstrated in any of the 30 patients. Six of the nine patients with primary amyloidosis exhibiting the most marked esophageal motor dysfunction had striking evidence of peripheral and/or autonomic nervous system involvement. No consistent pattern of motility disorder was observed in either group. The manometric abnormalities observed are consistent with a random deposition of amyloid in the esophagus involving a myopathic and/or neuropathic component.

Primary (AL) amyloidosis as a cause of breast masses.

Amyloidosis is rarely considered in the differential diagnosis of breast masses. During the past six years, 27 women with primary (24) and multiple myeloma-associated (three) amyloidosis (AL amyloid) were evaluated at our center. In five of these patients, amyloid was demonstrated on microscopic examination of breast tissue. The clinical presentations were similar to fibrocystic breast disease in two cases and malignancy in two others. Amyloidosis of the breast may be more common than previously recognized, especially considering the predilection of amyloid for depositing around fat cells. Therefore, pathologic examination of nonmalignant breast tissue should include Congo red staining and viewing under polarized light.

Familial amyloid polyneuropathy. Demonstration of prealbumin in a kinship of German/English ancestry with onset in the seventh decade.

A family with autosomal dominant transmitted familial amyloid polyneuropathy residing in Texas is described. Clinically, the prominent sensory and severe autonomic nervous system involvement resembles the Andrade (Portuguese) type I familial amyloid polyneuropathy but is unique in that the age of onset is in the seventh decade in all family members affected to date. Using an immunoperoxidase technique, prealbumin was demonstrated in the amyloid deposits. This finding suggests that this family shares biochemical as well as clinical characteristics consistent with similar kinships with type I familial amyloid polyneuropathy of diverse geographic origin.

Survival of patients with primary (AL) amyloidosis. Colchicine-treated cases from 1976 to 1983 compared with cases seen in previous years (1961 to 1973).

Primary amyloidosis has a variable course, but is generally associated with a short life expectancy. To date, no specific therapy has been available. Fifty-three patients with AL amyloidosis seen between 1976 and 1983 were treated with colchicine, and their clinical course and survival were compared with that in 29 other patients seen between 1961 and 1973. Of the variables measured, the treatment, the patient's sex, and the time interval from diagnosis to referral of treatment were significantly associated with length of survival. Median survival for the colchicine-treated patients was 17 months, compared with six months for the non-colchicine-treated patients. A surprising finding was the longer life span in female patients (median eight months versus four and a half months in the non-colchicine-treated group, and 25.5 months versus 10 month in the colchicine-treated group). The study suggests that colchicine has improved the life expectancy in AL amyloidosis. Although it is not a specific therapy, it may be a reasonable form of adjunctive treatment in this complex disorder.

Amyloid goiter: preoperative scintigraphic diagnosis using Tc-99m pyrophosphate.

Amyloid goiter is a rare clinical entity. The diagnosis is rarely made preoperatively because clinical and laboratory findings are nonspecific. We report two cases of amyloid goiter in whom the diagnosis was made preoperatively using Tc-99m pyrophosphate scintigraphy.

Sensitivity of technetium-99m-pyrophosphate scintigraphy in diagnosing cardiac amyloidosis.

To determine the value of technetium-99m-pyrophosphate myocardial scintigraphy in the diagnosis of amyloid heart disease this procedure was prospectively performed in 20 consecutive patients with biopsy-proven primary amyloidosis. Eleven patients had echocardiographic abnormalities compatible with amyloid cardiomyopathy, 9 of whom had congestive heart failure. Diffuse myocardial pyrophosphate uptake was of equal or greater intensity than that of the ribs in 9 of the 11 patients with echocardiograms suggestive of amyloidosis, but in only 2 of the 9 with normal echocardiograms, despite abnormal electrocardiograms (p less than 0.01). Increased wall thickness measured by M-mode echocardiography correlated with myocardial pyrophosphate uptake (r = 0.68, p less than 0.01). None of 10 control patients with nonamyloid, nonischemic heart disease had a strongly positive myocardial pyrophosphate uptake. Thus, myocardial technetium-99m-pyrophosphate scanning is a sensitive and specific test for the diagnosis of cardiac amyloidosis in patients with congestive heart failure of obscure origin. It does not appear to be of value for the early detection of cardiac involvement in patients with known primary amyloidosis without echocardiographic abnormalities.

Sensitivity and specificity of the echocardiographic features of cardiac amyloidosis.

Thirty-one patients with documented cardiac amyloidosis were compared to 39 control subjects with left ventricular hypertrophy to determine specific 2-dimensional echocardiographic features of amyloid. In 16 patients, increased myocardial echogenicity was present when a single short-axis view was examined, and had a sensitivity of 63% and a specificity of 74% for the diagnosis of amyloidosis. When complete echocardiograms were reviewed (15 patients), an improved sensitivity of 87% and specificity of 81% based on increased echogenicity was seen. Increased atrial septal thickness was present in 60% of amyloid patients and no controls. The combination of increased myocardial echogenicity and increased atrial thickness was 60% sensitive and 100% specific for the diagnosis of amyloidosis. The ratio of electrocardiographic voltage (S in V1 + R in V5 or V6) to left ventricular cross-sectional area also was examined. A ratio of less than 1.5 was 82% sensitive and 83% specific for amyloid (excluding the 2 patients with left bundle branch block), but added little to the diagnosis as determined from the 2-dimensional echocardiogram.

Molecular analysis of HLA class II genes in primary Sjögren's syndrome. A study of Israeli Jewish and Greek non-Jewish patients.

In an attempt to define the role of HLA class II genes in predisposition to primary Sjögren's syndrome, patients of two different ethnic groups (Israeli Jews and Greeks of non-Jewish origin) suffering from this disorder were studied. Oligonucleotide genotyping revealed the majority in both groups to carry either DRB1*1101 or DRB1*1104, alleles that are in linkage disequilibrium with DQB1*0301 and DQA1*0501. The high frequency of the two alleles in these SS patients is in contrast with the accepted association of primary SS with HLA-DR3 in Italian and American individuals. Molecular analysis of DQB1 and DQA1 alleles found in American Caucasian and American black SS (or SLE) patients demonstrated high frequencies of DQB1*0201 and DQA1*0501. The fact that the majority of SS patients, across racial and ethnic boundaries, carry a common allele, DQA1*0501, implies its involvement in the predisposition to primary SS. Based on sequence analysis and the computer imaging of the HLA class II molecule structure, a hypothetical model for the role of the DQ molecule in promoting primary SS is proposed.

Reactive arthritis associated with Clostridium difficile pseudomembranous colitis.

Reactive arthritis is associated with several gastrointestinal pathogens, particularly Shigella, Salmonella, Campylobacter, and Yersinia. Another, less well recognized bowel infection leading to reactive arthritis is pseudomembranous colitis, caused by Clostridium difficile. An illustrative case is presented, and the clinical features and characteristics of all reported patients with this association are reviewed. The pathogenesis of the reactive arthritis seems to be related to an immunological response in joints and other tissues against bacterial antigens, which gain access to the systemic circulation through increased intestinal permeability. Therapy with nonspecific antiinflammatory drugs, anticlostridial agents, or a combination of the above is effective. Despite the possibility of persistent articular involvement after gastrointestinal symptoms have subsided, the long-term prognosis seems to be excellent.

The use of oral pilocarpine in xerostomia and Sjögren's syndrome.

OBJECTIVES: To analyze the role of oral pilocarpine in the treatment of xerostomia of Sjogren's syndrome (SS). METHODS: The medical literature was reviewed for all studies using oral pilocarpine to treat xerostomia caused by SS or radiotherapy registered in the MedLine Silver Platter database from 1966 to 1998. RESULTS: All the studies identified excluded elderly individuals with cardiac or pulmonary disease. Patients with postradiation xerostomia and incomplete resection of the salivary glands were more likely to benefit from oral pilocarpine when there was sufficient residual glandular function than patients with radical surgery for head and neck cancer (HNC). However, patients with SS and other inflammatory disorders seemed to benefit from oral pilocarpine, when compared with patients with postradiation xerostomia. The optimal dose of oral pilocarpine, which was less likely to cause side effects, was 5 mg four times daily. A recent multi-center study in SS patients suggests that oral pilocarpine is effective and safe for long-term administration. Although some studies did not show evidence for increased salivary gland secretion rate as measured by sialometry, symptoms improved, perhaps because of increased secretion from the minor salivary glands or better conditioning of the oral mucosa. CONCLUSIONS: Oral pilocarpine is likely to benefit patients with SS by reducing the symptoms of xerostomia, even if the salivary gland secretion rate does not increase. Further controlled studies are needed in patients with SS and should include elderly patients with cardiovascular disease treated with moderate doses of oral pilocarpine.

Transformation of lymphoma to amyloidoma following radiation therapy.

A 62-year-old man presented with a localized upper-extremity small cell lymphoma with plasmacytoid features and an associated IgM lambda serum immunoglobulin level of 1,730 g/dl. The tumor was treated with 5,960 rad over 47 days. On completion of radiation therapy, the tumor had regressed only minimally, and the monoclonal immunoglobulin level had decreased by 63 per cent; repeat biopsy revealed that the lymphoma had been replaced by a virtually acellular mass of amyloid. It is postulated that radiation therapy accelerated the tissue conversion of lambda light chain into the beta-pleated sheet structure characteristic of amyloid fibrils.