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Dysphagia and Unexpected Myasthenia Gravis Associated with Primary Biliary Cirrhosis, Ulcerative Colitis and Vitiligo
... Although the development of extra intestinal manifestations during the course of IBD is well known, a controlled study indicated that 6.6% of UC patients and 1.9% of CD patients had at least 1 autoimmune disorder [5]. Cases of concomitant PBC and IBD are uncommon [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In addition, cases of concomitant PBC and CD appear to be extremely rare [21,22]; however, cases of concomitant PBC and UC have been sporadically reported [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. ...
... Cases of concomitant PBC and IBD are uncommon [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. In addition, cases of concomitant PBC and CD appear to be extremely rare [21,22]; however, cases of concomitant PBC and UC have been sporadically reported [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Currently, it is uncertain whether concomitant PBC and IBD occurs by chance or has a common immunological basis [21]. ...
... The characteristics of these 20 cases are summarized in Table 1. Of these, there were only 2 cases of concomitant PBC and CD and 18 cases of concomitant PBC and UC [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. ...
... There are 14 such cases reported to date in the English medical literature, in which MG was associated with any of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), or primary sclerosing cholangitis. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] The association with the overlap syndrome has been reported once. 15 ...
... In the previously reported cases, any one of AIH, PBC, or primary sclerosing cholangitis (clinically and/or histologically predominant) was associated with MG, both were usually diagnosed simultaneously but the liver disease could occur later (especially acute AIH) and responded poorly to treatment. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] All (except 1) were positive for AChR antibody, and all (except 2) had thymoma. 3,8 The unique feature in our case was the development of 2 autoimmune diseases such as MG 5 years after the diagnosis of overlap syndrome in the absence of anti-AChR and thymoma along with psoriasis. ...
The author presents a rare case of overlap syndrome associated with myasthenia gravis in the absence of acetylcholine receptor
antibody and thymoma. Various liver autoantibodies developed at different times later in the disease course and myasthenia
occurred 5 years after the diagnosis of liver disease. The importance of repeating antibody panel later in the disease course for proper
diagnosis and timely treatment is highlighted. The exact mechanism of the development of myasthenia gravis in autoimmune liver
disease also needs investigation for the possibility of new drug development that might be beneficial to both.(Full text available at journal website)
... Galbraith et al. reported a patient with MG who later developed ulcerative colitis (UC) and systemic lupus erythematosus [7], and other cases of MG with IBD have been reported [7][8][9][10][11][12], with MG being diagnosed both before and after IBD. Here, we present the clinical and electrodiagnostic findings of 2 patients with IBD who developed MG, from an IBD cohort that was established in 2004, and conducted a systematic literature review about the subject [3]. ...
... Our systematic literature review disclosed 15 papers and 21 patients with IBD and MG (Tables 1 and 2) [5,[7][8][9][10][11][12][14][15][16][17][18][19][20][21]. Sex and age were not detailed in some papers. ...
Co-morbid auto-immune disorders may affect 0.2% of the population. We present the clinical and electrodiagnostic findings of 2 patients with inflammatory bowel disease and myasthenia gravis from a Brazilian cohort of 218 inflammatory bowel disease patients. Patient 1: A 40 year-old man was diagnosed with ulcerative colitis at age 37 and underwent total colectomy 3 years later. After prednisone was tapered, he experienced a clinical relapse and was diagnosed with Crohn's disease. He then developed quadriparesis, bilateral ptosis, dysphagia and dysarthria. Patient 2: A 41 year-old woman (diagnosed with ulcerative colitis and primary sclerosing cholangitis at age 35) developed speech impairment and ptosis. On both patients, symptoms quickly progressed over few weeks. Myasthenia gravis was diagnosed and confirmed by abnormal repetitive nerve stimulation and elevated anti-acetylcholine receptor antibody titers. Pyridostigmine and prednisone successfully treated both patients. Myasthenia gravis prevalence over 9 years was 0.9%. Myasthenia gravis clinical course was not significantly modified by inflammatory bowel disease relapses and should be suspected with new onset weakness.
... Several autoimmune diseases can be concomitant to this pathology. Once the myasthenia gravis diagnosis is posed, an exhaustive research of autoimmune associated diseases is compulsory to have complete follow up of the patient [1]. We report the case of a 64-year-old man presenting an autoimmune hepatitis (AIH)-primary biliary cirrhosis (PBC) or an overlap syndrome concomitant with unexpected myasthenia gravis and thymoma. ...
... An early diagnosis permits to avoid many severe complications especially acute respiratory failure [2]. An expected case was published at 2004 demonstrating the association of atypical myasthenia, manifesting by a dysphagia, to a PBC, an ulcerative colitis and a vitiligo [1]. ...
The myasthenia gravis is an autoimmune disease which can be associated frequently with a thy-moma and also with autoimmune pathologies. We report the case of a 64-year-old man affected an overlap syndrome corresponding to the association of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). He also presented concomitant myasthenia gravis and thymoma. The physical examination notes only a disturbed voice. The liver tests showed: alkaline phosphatase 600 U/l, alanine aminotransferase 1280 U/l, and aspartate aminotransferase 985 U/l. Viral serol-ogies of hepatitis were all negative, as well as antinuclear, antimitochondrial and antismooth muscle antibodies. The diagnosis of an overlap syndrome was posed according to the biological and hepatic histhological results. An associated myasthenia was confirmed by the results of the EMG and the positivity of the anti-acetylcholine receptor antibody. A chest CT revealed a thymoma. The treatment consisted of ursodeoxycholic acid, prednisone, azathioprine and pyridostigmine. And the patient improved his voice and the liver function. Thymectomy was practiced without incidents .
... Autoimmune myasthenia gravis has been reported in a total of 24 IBD patients [10,[135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150]. A review of the literature, including 23 IBD patients, has found that in general myasthenia gravis was diagnosed several years after IBD, patients had other concomitant autoimmune disorders, pyridostigmine did not exacerbate diarrhea and other gastrointestinal symptoms, and thymectomy usually produced good results, improving both myasthenic and gastrointestinal symptoms [149]. ...
Inflammatory bowel diseases (IBD) are chronic inflammatory conditions affecting the digestive system, comprising two main distinctive entities, ulcerative colitis (UC) and Crohn's disease (CD). Besides gastrointestinal manifestations, IBD causes extraintestinal manifestations in the central and peripheral nervous system. The incidence of neurological complications in IBD ranges from 0.25% to 47.5%. The pathophysiology of neurological manifestations of IBD is mostly immune mediated, but dysfunction of the brain-gut axis, arterial and venous thromboembolism, infections, nutritional deficiencies and side-effects of medications (steroids, metronidazole, sulfasalazine, anti-TNF-α, anti-integrin antibodies) are other contributory mechanisms. Patients with IBD have an increased risk of arterial and venous stroke, mainly during periods of exacerbations. Vasculitis is extremely rare. There is a bidirectional association between multiple sclerosis and IBD, with a relative risk for comorbidity of 1.54, being 1.53 for the risk of multiple sclerosis in IBD and 1.55 for the risk of IBD in multiple sclerosis patients. Anti-TNF-α therapy is contraindicated in the treatment of patients who have both IBD and multiple sclerosis. Demyelinating disorders can also be a rare complication of anti-TNF-α therapy. Optic neuritis, transverse myelitis, progressive myelopathy, central nervous system infections, epilepsy and encephalopathy are among other uncommon neurological complications. Peripheral nervous system manifestations include peripheral neuropathy, either demyelination and axonal, myasthenia gravis and polymyositis/dermatomyositis and localized forms of myositis.
... Vitiligo has been rarely associated with PBC and PSC [232,233]. Myasthenia gravis and vitiligo have been described in a patient with PBC [234]. ...
Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.
... Intriguingly, two case reports of patients with MG and IBD describe clinical improvement of neuromuscular disease and IBD following different surgical procedures, one after thymectomy and the other following proctocolectomy. These reports emphasize the immunological link between MG and IBD [21,[70][71][72][73][74] . In addition to MG, cases of IBD associated with polymyositis or dermatomyositis have also been described [75][76][77] . ...
Only a very few systematic studies have investigated the frequency of neurologic disorders in patients with Crohn's disease (CD) and ulcerative colitis (UC), which are the two main types of inflammatory bowel disease (IBD). Results have been inconsistent and variable, owing to differences in case-finding methods and evaluated outcomes in different studies. The most frequent neurologic manifestations reported in CD and UC populations are cerebrovascular disease (with either arterial or venous events), demyelinating central nervous system disease, and peripheral neuropathy (whether axonal or demyelinating); however, the literature describes numerous nervous system disorders as being associated with IBD. The pathogenesis of nervous system tissue involvement in IBD has yet to be elucidated, although it seems to be related to immune mechanisms or prothrombotic states. The recently-introduced tumor necrosis factor (TNF) inhibitors have proven successful in controlling moderate to severe IBD activity. However, severe neurologic disorders associated with TNF inhibitors have been reported, which therefore raises concerns regarding the effect of anti-TNF-α antibodies on the nervous system. Although neurological involvement associated with IBD is rarely reported, gastroenterologists should be aware of the neurologic manifestations of IBD in order to provide early treatment, which is crucial for preventing major neurologic morbidity.
Background. Co-morbid auto-immune disorders may affect 0.2% of the population. We evaluated the association between myasthenia gravis and inflammatory bowel disease.
Methods. We present the epidemiological, clinical and electrodiagnostic findings of one patient with ulcerative colitis and three with Crohn’s disease (from a Brazilian cohort of 606 patients) and co-morbid myasthenia gravis.
Results.Mean age of onset of inflammatory bowel disease was 33.5+2.7, and patients are currently 45.8+7.3 years old. Two patients were acetylcholine receptor antibody positive, one anti-Muscle specific kinase positive and one seronegative. Three had abnormal repetitive nerve stimulation, all four had normal nerve conduction studies, abnormal skin wrinkling test and mild small fiber neuropathy. None had thymoma and/or accepted thymectomy. According to the Myasthenia Gravis Foundation classification, one was class V, one class IVb and two IIa. Myasthenia gravis diagnosis was masked by immunotherapy in all. The Prevalence ratio of having myasthenia gravis in inflammatory bowel disease patients in comparison with the proportion of myasthenia gravis among all patients seen in our center was 8.56 (P<0.0001, CI=3.1-23.5). Considering the lowest and highest prevalence of myasthenia gravis reported in the literature, the Prevalence ratio is 44.0 (P<0.0001, CI:16.3-118.4) and 26.4 (P<0.0001, CI: 9.8-70.6), respectively.
Conclusions. Myasthenia gravis prevalence is higher in inflammatory bowel disease and may include muscle specific kinase positive disease (first report in the literature). In general, myasthenia gravis clinical course was not significantly modified by inflammatory bowel disease relapses and frequently overlaps with other autoimmune conditions and small fiber neuropathy.
Background:
While the coexistence of vitiligo and Crohn's disease (CD) has been reported in individual patients, the epidemiological association between these autoimmune conditions remains inconclusive.
Objective:
To assess the bidirectional association between vitiligo and CD.
Methods:
A population-based study was performed to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting CD. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by multivariable Cox regression and logistic regression, respectively.
Results:
The incidence rate of new-onset CD was evaluated at 3.6 (95% CI, 2.7-4.9) cases per 10,000 person-years (PY) in patients with vitiligo and 2.4 (95% CI, 2.0-2.9) cases per 10,000 PY in controls. Patients with vitiligo experienced an elevated risk of CD (fully adjusted HR, 1.60; 95% CI, 1.10-2.34; p = 0.015). Congruently, a history of preexisting CD predicted elevated odds of having subsequent vitiligo (fully adjusted OR, 1.49; 95% CI, 1.15-1.93; p = 0.002). Compared to other patients with vitiligo, those with vitiligo and comorbid CD were older and had a higher prevalence of diabetes mellitus, hyperlipidemia, and hypertension but a comparable all-cause mortality rate.
Conclusions:
The current study depicts a robust bidirectional association between vitiligo and CD. This knowledge is of clinical implication for physicians managing patients with both conditions. The diagnostic threshold for CD should be lowered in vitiligo patients with compatible symptoms.
Co-morbid auto-immune disorders may affect 0.2% of the population. We present the clinical/electrodiagnostic findings of 2 patients with inflammatory bowel disease and myasthenia gravis from a Brazilian cohort of 218 inflammatory bowel disease patients. Patient 1: A 40 year-old man was diagnosed with ulcerative colitis at age 37 and underwent total colectomy 3 years later. After prednisone was tapered, he experienced a clinical relapse and was diagnosed with Crohńs disease. He then developed quadriparesis, bilateral ptosis, dysphagia and dysarthria. Patient 2: A 41 year-old woman (diagnosed with ulcerative colitis and primary sclerosing cholangitis at age 35) developed speech impairment and ptosis. On both patients, symptoms quickly progressed over few weeks. Myasthenia gravis was diagnosed and confirmed by abnormal repetitive nerve stimulation and elevated anti-acetylcholine receptor antibody titers. Pyridostigmine and prednisone successfully treated both patients. Myasthenia gravis prevalence over 9 years was 0.9%. Myasthenia gravis clinical course was not significantly modified by inflammatory bowel disease relapses and should be suspected with new onset weakness.
Con il termine disfagia si defi-nisce la difficoltà riferita dal pa-ziente nell'atto di deglutire so-stanze liquide o solide 1 . La dia-gnosi discende da un'accurata indagine anamnestica attuata me-diante questionari standardizza-ti 2 , attraverso cui è possibile diffe-renziare la disfagia esofagea ri-spetto a quella orofaringea. Molti studi descrivono la presenza di questo sintomo in presenza di pa-tologie esofagee 3-9 , oppure per ma-lattie del distretto orofaringeo 10-14 . Riassunto. La disfagia, definita come difficoltosa deglutizione di sostanze fluide e solide, è uno dei sintomi che ricorre con maggiore frequenza in patologie esofagee o più in generale del distretto gastrointestinale ed otorinolaringoiatrico. Anche numerose patologie del cavo orale riconoscono come sintomo comune, sia nelle fasi precoci che in quelle tardive, la diffi-coltà a deglutire e ciò può verificarsi in presenza di lesioni ad eziopatogenesi molto diverse: evento flogistico transitorio ad eziologia traumatica, patologia immunomediata o infettiva, neoplasia maligna o ancora mucositi in corso di chemio-radioterapia. L'intensità del distur-bo e più in generale l'espressione clinica di questo sintomo così comune, in associazione alla presenza di lesioni più o meno evidenti in corrispondenza delle mucose del cavo orale, do-vrebbero suggerire la presenza di una patologia del distretto orofarigeo o di distretti vicini, consentendo in tempi brevi interventi diagnostico-terapeutici mirati. Gli autori descrivono gli aspetti clinici ed eziopatogenetici delle patologie della mucosa orale che più frequente-mente possono esprimersi attraverso il sintomo della disfagia e le caratteristiche cliniche ed epidemiologiche più importanti di patologie sistemiche che presentano questo disturbo a lo-calizzazione orale, suggerendo un possibile approccio odontostomatologico per la disfagia. Parole chiave. Disfagia, lesioni orali, patologie sistemiche.
Primary Biliary Cirrhosis and Myasthenia Gravis are both autoimmune conditions, however, there are only rare case reports of their association. This is a case report of acetylcholine receptor antibody positive generalized myasthenia gravis in a female patient with antimitochondrial antibody positive, liver biopsy-confirmed primary biliary cirrhosis.
A very uncommon case report of a young woman suffering from multiple autoimmune-dysreactive disorders (including thyroiditis, myasthenia gravis, Crohn's disease, and erythema nodosum), while undergoing steroideal therapy, was complicated by a severe upper urinary tract infection. The pathogenetic and clinical association between the different autoimmune-dysreactive complications deserves discussion, as well as the eventual supporting role of the immunosuppressive treatment, which might contribute significantly to these risk factors. Clinicians who are engaged in the management of these patients should be aware that multiple, concurrent or subsequent disorders may occur in these subjects, and also severe infectious complications may be of relevant concern.
Dysphagia, defined as a difficulty in swallowing of fluids and/or food, is one of the most frequent symptoms of oesophageal, gastrointestinal or ENT diseases. Interestingly, dysphagia can be also the initial or late symptom of several oral diseases: e.g. traumatic ulcerations, immunomediated or infectious lesions, malignant neoplastic disease or mucositis in chemio-radiotherapy. The presence of this frequent symptom, with or without oral evident lesions, can suggest the presence of oral or perioral diseases, promoving adequate diagnostic-therapeutic management. In this paper, authors describe aetiology, pathogenesis and clinical aspects of oral diseases, as being more frequently associated with dysphagia; moreover, they describe the most important clinical and epidemiological features of systemic diseases associated with dysphagia.
The case of a young woman suffering from multiple autoimmune-dysreactive disorders (including thyreoiditis, myasthenia gravis, thymectomy, Crohn's disease, and erythema nodosum), while undergoing steroideal therapy, was complicated by a severe infectious disorder (severe upper urinary tract infection). While the pathogenetic and clinical relationship between the different autoimmune-dysreactive complications is still unclear, and the supporting role of the frequent immunosuppressive treatment may add significantly to these risk factors, clinicians who are engaged in the management of these patients should be aware that multiple, concurrent or subsequent disorders might occur in these subjects, and also that severe infections might be of relevant concern.
The incidence and prevalence of collagenous colitis are unknown. An epidemiological study was undertaken between 1984-93. All patients living in the immediate catchment area of Orebro Medical Center Hospital with the diagnosis collagenous colitis were identified. Biopsy specimens classified as unspecific intestinal fibrosis were re-examined to identify cases not correctly diagnosed at first. Medical records were scrutinised and colorectal biopsy specimens re-evaluated. Thirty patients with collagenous colitis were diagnosed during the study period. The female:male ratio was 9:1. The median age at diagnosis was 64 (28-78) years. The prevalence at 31 December 1993, was 15.7/10(5) inhabitants (95% CI; 9.8 to 21.6/10(5)). The mean annual incidence during the period 1984-93 was 1.8/10(5) inhabitants (95% CI; 1.2 to 2.4/10(5)). A peak incidence was found in women 70-79 years old. Collagenous colitis occurs mainly in middle aged women, and the frequency is higher than earlier anticipated. The prevalence and incidence is similar to primary biliary cirrhosis. In women 70-79 years of age, the incidence for collagenous colitis approaches the incidence for ulcerative colitis.
Data on collagenous colitis have been based on a limited number of patients.
To obtain more information on this disease from a register set up at Orebro Medical Center Hospital.
Twenty five Swedish hospitals have contributed to this patient register, which comprises 163 histopathologically verified cases. Clinical data were retrospectively analysed.
Collagenous colitis followed a chronic intermittent course in most cases (85%) with a sudden onset in 42%. Symptoms were chronic watery diarrhoea, often nocturnal (27%), abdominal pain (41%), and weight loss (42%). Sixty six patients (40%) had one or more associated diseases. Routine laboratory data were mostly normal. The median age at diagnosis was 55 (range 16-86) years, but 25% of the patients were younger than 45 years. Seven patients died of unrelated diseases. The response rate for sulphasalazine was 59%, and 50% and 40% for mesalazine and olsalazine. Prednisolone was most effective with a response rate of 82%, but the required dose was often high and the effect was not sustained after withdrawal. Antibiotics were efficient in 63%. Cholestyramine and loperamide had response rates of 59% and 71% respectively.
Collagenous colitis follows a chronic continuous course. Symptoms can be socially disabling, but the disease does not seem to have a malignant potential. A plan for the treatment of a newly diagnosed patient with collagenous colitis is proposed.
Collagenous colitis is a recently described form of chronic inflammatory bowel disease. Other inflammatory bowel disorders are associated with increased risk of colorectal and extracolonic malignancies, but this has not been evaluated in collagenous colitis. Colorectal and extracolonic malignancies were identified in 117 patients with collagenous colitis from the Johns Hopkins Registry. The incidence rates of identified tumors, overall incidence rate of tumors, and overall mortality were then compared with general population through person year analysis with adjustment for population. No cases of colorectal cancer were found in collagenous colitis patients during a mean follow-up period of 7.0 years (range 2-12 years) after the diagnosis of colitis. Two patients developed colorectal cancer prior to the diagnosis of colitis, but no increase in lifetime relative risk of colorectal cancer was found (relative risk 0.52, 95% confidence limits 0.05-1.5). An increased relative risk of lung cancer in women (relative risk 3.7: 95% confidence limits 1.0-9.6: p = 0.048) was noted. The relative risk of overall malignancy and overall mortality was not different than the general population. In collagenous colitis patients the life time relative risk of colorectal cancer and the relative risk after the diagnosis of colitis with a mean observation period of 7 years was not increased. An increase in relative risk of lung cancer in women with collagenous colitis argues for further investigation of the role of smoking and other factors in this disorder.
Background: The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B 12 status. Elevated homocysteine concentrations are associated with an increased risk for vascular disease. Objective: To identify reference ranges for serum total homocysteine concentration in U.S. residents and quantify the contribution of circulating vitamin concentrations to high homocysteine concentrations. Design: Cross-sectional prevalence study. Setting: United States. Patients: A nationally representative sample of 3563 male participants and 4523 female participants 12 years of age or older who participated in the third National Health and Nutrition Examination Survey. Measurements: Reference ranges (5th and 95th percentiles) for the total homocysteine concentration were defined among participants who were folate- and vitamin B 12 -replete and had normal creatinine concentrations. A high total homocysteine concentration was defined as one that exceeded the sex-specific 95th percentile for the reference sample (participants 20 to 39 years of age). The population attributable risk percentage was calculated to determine the contribution of low folate (<11 nmol/L) and vitamin B 12 (<185 pmol/L) concentrations to a high homocysteine concentration. Results: Reference ranges for serum total homocysteine concentration increased with age; these ranges were 4.3 to 9.9 μmol/L for male participants and 3.3 to 7.2 μmol/L for female participants 12 to 19 years of age and from 5.9 to 15.3 μmol/L for men and 4.9 to 11.6 μmol/L for women 60 years of age or older. A high homocysteine concentration was defined as at least 11.4 μmol/L for male participants and at least 10.4 μmol/L for female participants. Approximately two thirds of the cases of high homocysteine concentrations were associated with low vitamin concentrations. Conclusions: Upper reference limits for the serum total homocysteine concentration increased with age and were higher for male participants than for female participants at all ages. In most cases, high homocysteine concentrations were associated with low serum vitamin concentrations.
With great interest, we read the recent article by Bernard et al¹ in the January 1995 issue of the Archives on the incidence and distribution of subepidermal autoimmune bullous skin diseases in three French regions. Epidemiologic data on these conditions had been extremely rare, and we undertook a similar study in the Department of Dermatology at the University of Würzburg (Germany). This center is the only dermatologic department in northwestern Bavaria, a region of central Germany. The observation period was 65 months (March 1989 through July 1994), and cases included in this investigation came from an area covering a population of 1.7× 10⁶.
All patients in this study suffered from a newly acquired bullous disease involving the skin and/or the mucous membranes. These patients were seen in our outpatient clinic, and most were admitted for initiation of treatment. The diagnostic criteria are shown in Table 1. All patients
Background
The epidemiology of bullous pemphigoid (BP) is not clear because of the heterogeneity of the disease, and its possible association with internal malignancies has been under debate for many years. We report the findings of a 2-year study on incident BP cases in the Liguria region of Italy.Subjects and methodsThirty-two patients with BP were collected over the 2-year period. Diagnosis was made based on clinical findings and confirmed by histology, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) with salt-split skin and monkey oesophagus, and immunoblotting (IB). All patients were thoroughly investigated for possible malignancies and all were followed up for 6 months to monitor the response to treatment.ResultsDIF showed linear deposits at the dermoepidermal junction in all but one patient. IIF gave positive findings for 15 sera tested with monkey oesophagus and 20 tested with salt-split skin. IB gave positive findings in 19 cases. There was a malignancy in six cases, but no clinical or immunological features that could be considered to predict this occurrence.Conclusions
The findings of this study are in accordance with most of the data found in the literature, including the fact that IgG serum levels did not predict the course of the disease. Contrary to previous indications, IgE levels were not indicative of disease course either. Mucosal lesions, erythema multiform-like lesions, negative IIF findings and antibodies to AgPB2 were not a prediction for the development of malignancy.
Serum homocysteine is increased, and correlates inversely with cognitive scores, in Alzheimer’s disease (AD), vascular dementia and ‘age-associated memory impairment’. Elevated levels might signal accelerated cognitive decline, although this remains to be established. We therefore repeated Mini-Mental State Examinations, together with additional ADAS-Cog assessments, in 32 healthy elderly individuals to determine whether prior homocysteine levels predicted cognitive changes over a 5-year period. Homocysteine predicted follow-up cognitive scores and rate of decline in cognitive performance independently of age, sex, education, renal function, vitamin B status, smoking and hypertension (p < 0.001). Homocysteine predicted word recall (p = 0.01), orientation (p = 0.02) and constructional praxis scores (p < 0.0001). One subject, with the second highest initial homocysteine, had developed probable AD at follow-up. Fasting total serum homocysteine appears to be an independent predictor of cognitive decline in healthy elderly and exerts a maximal effect on spatial copying skills.
This article provides an overview of how peroxidation of unsaturated lipids takes place and how it can be measured. Several different aspects of free-radical-mediated lipid peroxidation are discussed, including: (a) the catalytic role of chelated iron and other redox metal ions; (b) induction by reducing agents such as superoxide, ascorbate, and xenobiotic free radicals; (c) suppression by antioxidant chemicals and enzymes; and (d) how peroxidation that depends on pre-existing hydroperoxides (lipid hydroperoxide-dependent initiation of lipid peroxidation) can be distinguished from that which does not (lipid hydroperoxide-independent initiation of lipid peroxidation). Attention is also given to non-radical, singlet oxygen-driven peroxidation and how this can be resolved from radical-driven processes.
Amongst the focal and multifocal neuropathies that are associated with diabetes mellitus one of the most common is a proximal predominantly motor lower limb neuropathy. Recent evidence has indicated that, at least in a proportion of cases, this may have an inflammatory basis. We have examined a consecutive series of 15 cases of proximal diabetic neuropathy (diabetic amyotrophy). These were characterized by proximal pain and asymmetric proximal or generalized lower limb muscle weakness, associated in some cases with radicular sensory involvement. Two-thirds of the patients had an accompanying distal symmetric sensory polyneuropathy. Biopsy of the intermediate cutaneous nerve of the thigh, a sensory branch of the femoral nerve, showed epineurial microvasculitis in 3 patients and nonvasculitic epineurial inflammatory infiltrates in another case. In a further case, microvasculitis was found in both in the sural nerve and a quadriceps muscle biopsy specimen. The detection of inflammatory changes appeared to be correlated with the occurrence of sensory radicular involvement. Whether similar changes are present in muscle nerves in this predominantly motor syndrome requires further study. Nevertheless, the present observations confirm the view that secondary vasculitic or other inflammatory reactions may contribute to some forms of diabetic neuropathy.
A case of chronic watery diarrhoea showed in rectal biopsy a thick subepithelial collagenous deposit in the colorectal mucosa. This deposit was of the same type as that described in the jejunal mucosa in collagenous sprue, and seems to have been the cause of the diarrhoea.
The use of oral non-steroidal anti-inflammatory drugs (NSAIDs) in 31 patients with collagenous colitis and in 31 matched control patients with irritable bowel syndrome or colonic diverticular disease who had also undergone colonoscopy and biopsy was investigated. The long term use (greater than 6 months) of NSAIDs was significantly commoner in the study group (19/31) than in the control group (4/31) (p less than 0.02), even assuming the most adverse drug history in six patients in whom this could not be established. In all patients with collagenous colitis taking NSAIDs, diarrhoea followed the use of these drugs, and by a mean (SD) of 5.5 (4.4) years (range 0.5 to 15 years). In three patients with collagenous colitis, diarrhoea improved after withdrawing NSAIDs; rechallenge in one was followed by a recurrence of diarrhoea, which improved after withdrawing the drug again. It is suggested that NSAIDs may play an aetiological role in the diarrhoea and thickened collagen band in some patients with collagenous colitis.
Auto-antibodies against the acetylcholine receptor of skeletal muscle are considered to be the cause of the neuromuscular dysfunction in myasthenia gravis. However, such auto-antibodies also occur in disease states not accompanied by neuromuscular symptoms. Patients with primary biliary cirrhosis have a high prevalence of different auto-antibodies, including antibodies against the acetylcholine receptor. In primary biliary cirrhosis, these anti-receptor antibodies are predominantly of IgM isotype. The IgM antibodies show a broader reactivity with receptors from other species than antibodies from myasthenic patients. Immunoglobulins from patients with primary biliary cirrhosis bear the same receptor antibody-associated idiotypes, but the repertoire is quantitatively different from that found in myasthenia gravis patients. The IgM receptor antibody activity in a serum from a patient with primary biliary cirrhosis could be inhibited by cardiolipin, poly[dT], poly[I], and ssDNA, whereas this antibody activity in serum from a patient with myasthenia gravis was slightly reduced only by cardiolipin. Generally, IgM antibodies from patients with primary biliary cirrhosis had a broader reactivity with polynucleotides and phospholipids than IgG antibodies and antibodies from patients with myasthenia gravis. These results indicate a difference in the fine specificity between acetylcholine receptor antibodies in primary biliary cirrhosis and in myasthenia gravis.
Antibodies against the acetylcholine receptor were found in a patient with primary biliary cirrhosis. The patient had no clinical or electrophysiological evidence of disturbed neuromuscular function. The antibodies were of both IgG and IgM isotype. Following passive transfer, these antibodies showed the same capacity to bind in vivo to mouse muscle receptors as immunoglobulins from patients with myasthenia gravis. The affinity of the antibodies was high and comparable to that found in myasthenia gravis patients.
Antibodies binding to the acetylcholine receptor of human skeletal muscle were found in patients with different kinds of anti-mitochondrial antibodies. In patients with primary biliary cirrhosis (PBC), the antibody activity was found in monomeric and pentameric IgM as well as in IgG, whereas patients with other kinds of anti-mitochondrial antibodies had anti-receptor antibodies of predominantly IgG class. Mice transfused with immunoglobulins from patients with PBC showed a reduction of skeletal muscle receptors comparable to that found in mice who had received immunoglobulins from myasthenia gravis (MG) patients. The antibody affinity was of the same order of magnitude in MG and PBC but antibodies with multiple affinities were more common in PBC. In PBC, the anti-receptor antibody associated idiotype repertoire was markedly different from that found in MG.
Sundewall A-C, Lefvert AK, Olsson R. (Department of Clinical Chemistry, Huddinge University Hospital, Huddinge, and Department of Medicine II, Sahlgrenska University Hospital, Gothenburg, Sweden.) Anti-acetylcholine receptor antibodies in primary biliary cirrhosis.
Low concentrations of acetylcholine receptor antibodies were found in 16 out of 17 patients with primary biliary cirrhosis. Seven patients were treated or had been treated with penicillamine. Ten untreated patients had antibody levels corresponding to those found in the treated group. Our data support the presence of receptor antibodies of both IgG and IgM class.
The Index of Independence in Activities of Daily Living (ADL), now in frequent use in rehabilitation settings, has application for prevention of disability and maintenance of rehabilitation gains in the aging person in all settings. Since the Index is sensitive to changes in meaningful self-care functions, uses well-defined criteria, and can be broadly taught to non-professionals, it has considerable practical value as a longitudinal measure of change and predictor of adaptive capacity in terms of community residences and congregate living facilities.
Information was obtained by questionnaire about 215 nonhemophilic patients who developed inhibitors against factor VIII (antihemophilic factor). The majority of the patients were over 50 years of age, and approximately equal numbers of males and females were reported. Rheumatoid arthritis was present in 8% of the cases, 7% occurred during pregnancy or the post-partum period, and in several there was an association with allergy to penicillin, asthma, “auto-immune” diseases, or malignancy. In 46% of cases, no underlying disorders were identified. Major bleeding was observed in 87 % of patients, and in 22%, death was attributed either directly or indirectly to the presence of the inhibitor.
In 11 of 31 patients receiving no therapy other than supportive transfusions of blood or factor VIII concentrate, the inhibitor disappeared after being present for an average duration of 14 months. Corticosteriods were thought to be effective in abolishing the inhibitor in 22 of 45 patients in whom these were the only drugs administered. Twenty-eight patients received azathioprine as well as corticosteriods; in 19, the inhibitor declined or disappeared during treatment. Finally, 80 patients were treated with cyclophosphamide; in 37 there was a favorable outcome. Inhibitors in children and post-partum patients were more likely to disappear spontaneously or with steroid therapy, whereas those in patients with rheumatoid arthritis or other “autoimmune” disorders required treatment with alkylating agents. However, before any specific therapy can be recommended for this disorder, prospective trials of potential therapeutic agents should be conducted in selected subgroups.
WITHIN the past decade and particularly within the past 5 years, an unusual form of hyperthyroidism has received increasing attention (1–22). The hyperthyroid manifestations are generally self limiting, although some cases relapse, are accompanied by chronic inflammatory changes within the thyroid parenchyma, and are marked by a very low 131I uptake. Despite the usually abrupt onset of symptoms and the diffuse lymphocytic infiltration, thyroidal pain and/or tenderness is completely absent. Because this syndrome overlaps many of the features of both lymphocytic thyroiditis and subacute thyroiditis, there has been much debate about how to categorize it or whether to consider it a new disease entity. Nomenclature used by the several groups describing it includes: painless thyroiditis (7, 11, 17, 20), silent thyroiditis (3, 9, 19, 22), occult subacute thyroiditis (1), painless subacute thyroiditis (10, 14), subacute nonsuppurative thyroiditis (2), atypical (“silent”) subacute thyroiditis (16), lymphocytic thy...
To determine the frequency of patchy colonic involvement, fecal leukocytosis, and association with celiac sprue in a large cohort of patients with collagenous colitis.
We conducted a retrospective review of the medical records of 172 consecutive Mayo Clinic patients in whom collagenous colitis had been diagnosed between 1982 and 1993.
For each of the 172 patients, the medical record was reviewed to determine the frequency of (1) fecal leukocytosis; (2) characteristic histologic findings in the rectum and the sigmoid, descending, and ascending colon; and (3) small bowel biopsy findings consistent with celiac sprue.
The presence of fecal leukocytes was noted in 64 of 116 patients (55%) who had undergone assessment for fecal leukocytosis. On analysis of histologic findings, 113 of 123 rectal, 116 of 121 sigmoid, and 68 of 70 descending colon biopsy specimens were diagnostic of collagenous colitis. Small bowel biopsies were performed in 45 patients who did not have a history of small intestinal disease: 1 had celiac sprue and 44 had normal findings. Two other patients had previously diagnosed celiac sprue.
The finding of fecal leukocytes in 55% of patients with collagenous colitis confirms the inflammatory basis of this disease. Biopsy specimens obtained by flexible sigmoidoscopy seem sufficient to establish the diagnosis in most patients, and colonoscopic biopsy of the more proximal area of the colon is usually unnecessary. Celiac sprue infrequently accompanies collagenous colitis; thus, routine small bowel biopsy is not warranted.
Measurements of the serum concentrations of the metabolites homocysteine, cystathionine, methylmalonic acid, and 2-methylcitric acid, which accumulates when vitamin B-12-, folate-, and vitamin B-6-dependent enzymatic reactions are impaired, should provide a better indication of intracellular deficiency of these vitamins. We measured the serum concentration of these vitamins and the four metabolites in 99 healthy young people, 64 healthy elderly subjects, and 286 elderly hospitalized patients. A low serum vitamin B-12 concentration was found in 6% and 5%, low folate in 5% and 19%, and low vitamin B-6 in 9% and 51%, and one or more metabolites were elevated in 63% and 83% of healthy elderly subjects and elderly hospitalized patients, respectively. These results strongly suggest that the prevalence of tissue deficiencies of vitamin B-12, folate, and vitamin B-6 as demonstrated by the elevated metabolite concentrations is substantially higher than that estimated by measuring concentrations of the vitamins.
To evaluate the significance of the association of malignancy with autoimmune blistering diseases, we studied the incidence of internal malignancies in 496 pemphigus and 1,113 bullous pemphigoid (BP) patients in Japan. Statistical analysis showed that an association ratio of internal malignancies with pemphigus was 5.0% and that with BP was 5.8%. These ratios were significantly higher than that of the controls aged over 70 years (0.61%). Our results indicate that detailed examination for internal malignancy is essential for patients with pemphigus or BP.
Influenza vaccination is a widely accepted practice particularly among the elderly and high risk individuals. Minor and transitory side effects following the vaccination are common while systemic complications are infrequently reported. We describe 3 patients who developed systemic vasculitis following influenza vaccination. With increasing use of influenza vaccination, attention should be drawn to the possible expression of systemic adverse effects such as vasculitis.
The role of functional and cognitive limitations in the risk of pneumonia-related mortality in older adults was examined. As part of a cohort study in 3 communities (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA), 6,234 women and 4,035 men ages 65 or older completed baseline interviews between 1981 and 1983 and were followed for up to 6 years. Sex-specific Cox proportional-hazards regression models were used to examine the association of baseline physical and cognitive functioning with report of pneumonia (ICD9 480-486) as an underlying, immediate, or contributing cause of death. During followup, a total of 243 men and 160 women died with pneumonia. Adjusting for age, race, education, evidence of five chronic diseases, and smoking status, a significantly increased risk of pneumonia mortality (P < 0.05) was found for limitations in activities of daily living and cognitive impairment among both men and women. Inability to walk a half mile, climb stairs, or perform heavy housework was significantly associated with increased risk of pneumonia mortality for women but not for men in the same multivariate models. Men and women whose body-mass index was above the median had significantly lower risk of pneumonia mortality compared with those in the lowest quartile. Further elucidation of the sequence between physical and cognitive impairment and risk of pneumonia will be important in reducing pneumonia-associated morbidity and mortality.
The frequency of HLA-DRB1 alleles was determined in 68 Caucasoid patients with polymyalgia rheumatica (PMR) and 140 controls
using polymerase chain reaction (PCR) sequence-specific oligonucleotide typing. In keeping with previous studies, an increased
frequency of DRB1*04 was observed in patients [55.9% vs 35.0%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3–4.4]. HLA-DRBl*0101 frequency was also increased in patients, although less confidence could be placed on this association (19.1% vs 14.3%, OR 1.4,95% CI 0.6–3.3). HLA-DRB1*O4 subtyping indicated that the frequencies of both DRB1*0401 (38.2% vs 22.1%, OR 2.2, 95% CI 1.0–4.3) and DRB1*0404 (16.2% vs 5.0%, OR 3.7, 95% CI 1.2–11.1) were specifically raised. An increased frequency of the RA shared epitope (QKRAA/QRRAA) was
also observed in this group (75.0% vs 44.2%, OR 3.8, 95% CI 1.9–7.6). When the analysis was restricted to only DRB1*04-negative patients and controls, the frequencies of DRB1*0301, *11 and *08 were marginally raised. However, no obvious relationship appeared to exist between PMR susceptibility and DRB1 alleles
carrying the DYF conserved epitope in the second hypervariable region. Autoantibodies to thyroid antigens were present in
23% of patients. An increased frequency of DRBl*0301 was observed in patients with thyroid microsomal antibodies compared to those without (54.5% vs 24.6%, OR 3.7, 95% CI 0.8–17.0). This increase was not observed in patients with thyroglobulin autoantibodies. These data
indicate that both DRB 1*0401 and *0404 are associated with PMR, and that this may extend to include DRB1*0101. The immunogenetic profile of susceptibility markers in this condition appears to be similar to that in rheumatoid arthritis.
A 43-year-old woman with recently diagnosed primary biliary cirrhosis developed antibody-negative myasthenia gravis. She did not receive D-penicillamine therapy. Clinical and immunological features of this patient are discussed. In previous reports on an association between primary biliary cirrhosis and myasthenia D-penicillamine treatment was an obligate causal linkage between both disorders.
The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r = -0.70, p < 0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-1-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.
Collagenous colitis is a chronic diarrheal disease characterized by a normal or near-normal mucosa endoscopically and microscopic inflammation in the lamina propria, surface epithelial injury and a thick subepithelial collagen layer. The symptoms of collagenous colitis vary in duration and intensity, and long periods of remission have been described, but long-term follow-up data are limited. Our goal was to determine the natural clinical history of collagenous colitis and to determine whether there was a relationship between histopathologic changes and course of disease.
Cases were identified at the University of Michigan Hospitals using surgical pathology records before 1992. All charts, including medical records from other hospitals, were reviewed, and a telephone interview was conducted with each locatable patient (pt). Biopsy specimens were reviewed by two pathologists for degree of collagen layer thickness, epithelial damage, and inflammation.
There were 31 patients (26 F, 5 M) with a mean age of 66 yr (range 33-83) and a mean duration of symptoms of 5.4 yr at the time of diagnosis. Of the 31 patients, 18 (56%) had some form of arthritis, and 22 (71%) were using NSAIDS regularly at the time of diagnosis. Follow-up interviews were conducted at least 2 yr after diagnosis (mean 3.5 yr, range 2-5 yr) with 27 of 31 patients (3 could not be located, 1 died). Two definable groups of patients were identified: (1) those with either spontaneous or treatment-related symptom resolution (63%), and (2) those with ongoing or intermittent symptoms requiring at least intermittent therapy (37%). There was no significant difference between the two groups with regard to sex, age, associated diseases, and use of medications. Patients with symptom resolution (mean duration 3.1 yr) had been treated with antidiarrheals (6), sulfasalazine (3), discontinuation of NSAIDS (3), reversal of jejunoilial bypass (1), or nothing (4). Those with ongoing symptoms experienced a wide range of symptom severity. Two required only antidiarrheals, but five required or failed steroids, azathioprine, or sandostatin. There was no significant difference in collagen thickness, epithelial damage, and inflammation between the two groups, but Paneth cell metaplasia was seen more often in those with ongoing symptoms. In 24 of 27 patients, diagnostic changes were present in left-sided biopsies.
In our cohort of patients, 63% had lasting resolution of symptoms after a mean 3.5 yr follow-up. There was a high incidence of arthritis and NSAID use in our population, but there was no relationship between these entities and clinical course or histology. Initial histology, except possibly for Paneth cell metaplasia, did not reliably predict severity or course of disease. Finally, although variable in clinical presentation, treatment-free remissions are common in collagenous colitis.
Autoimmune diseases cause significant and chronic morbidity and disability. The actual number of persons in the United States that are affected by autoimmune diseases and the resultant magnitude of their impact on the public's health are limited to a few specific diseases. In order to understand the clinical, public health and economic importance of these diseases it is necessary to have estimates of incidence and prevalence rates in the population. In this analysis, we estimate the number of persons affected by 24 autoimmune diseases in the United States by applying mean weighted prevalence and incidence rates obtained from published articles to U. S. Census data. The study was restricted to 24 autoimmune predefined diseases for which there was direct or indirect evidence for autoimmune pathogenesis. Subsequently, we used computerized search software and ancestry searching (bibliographies) to conduct a comprehensive search of articles published from 1965 to the present. Eligible studies included those which adhered to standard disease definitions and which included population-based estimates of incidence or prevalence rates. Mean weighted incidence and prevalence rates were calculated from eligible published studies with greater weight proportionately given to larger studies. The mean rates were then applied to the U.S. Census population figures to estimate the number of persons currently afflicted with each disease and the number of new cases occurring each year in the United States. Only U.S. and European studies were used to estimate prevalence and incidence rates when there were at least six eligible studies available for a disease. When there were fewer than six studies, all available studies were included, regardless of country of origin. The number of eligible incidence and prevalence studies found in the literature varied considerably between the 24 autoimmune diseases selected. The largest number of eligible prevalence studies were conducted on multiple sclerosis (MS), rheumatoid arthritis, and systemic lupus erythematosus (SLE) (>/=23), followed by insulin-dependent diabetes (IDDM), myasthenia gravis, primary biliary cirrhosis, and scleroderma (>/=7). There were only one to four eligible studies done on 11 other diseases, and no prevalence studies on 6 diseases. Incidence studies were less frequent but the largest number of studies were conducted on IDDM (n = 37) and MS (n = 28), followed by Graves' disease/hyperthyroidism, glomerulonephritis, primary biliary cirrhosis, rheumatic fever, rheumatoid arthritis, scleroderma, and SLE (>/=9). On the other 11 diseases, there were one to six eligible studies, and no studies on 5 diseases. There were no eligible incidence or prevalence studies on Goodpasture's syndrome, idiopathic thrombocytopenia purpura, or relapsing polychondritis. Overall we estimate that 8,511,845 persons in the United States or approximately 1 in 31 Americans are currently afflicted with one of these autoimmune diseases. The diseases with the highest prevalence rates were Graves'/hyperthyroidism, IDDM, pernicious anemia, rheumatoid arthritis, thyroiditis, and vitiligo, comprising an estimated 7,939, 280 people or 93% of the total number estimated. Glomerulonephritis, MS, and SLE added an estimated 323,232 people. The prevalence of the other diseases reviewed were rare, less than 5.14/100,000. Most diseases were more common in women. From the incidence data we estimate that 237,203 Americans will develop an autoimmune disease in 1996 and that approximately 1,186,015 new cases of these autoimmune diseases occur in the United States every 5 years. Women were at 2.7 times greater risk than men to acquire an autoimmune disease. After reviewing the medical literature for incidence and prevalence rates of 24 autoimmune diseases, we conclude that many autoimmune diseases are infrequently studied by epidemiologists. As a result the total burden of disease may be an underestimate. (ABSTRACT TRUNCATED)
Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients receiving or not receiving inhaled corticosteroids and in nonsmoking and smoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids (5.6+/-0.6 ppm, p < 0.001) and similar in asthmatic patients receiving inhaled corticosteroids (1.7+/-0.1 ppm) compared with those in nonsmoking healthy control subjects (1.5+/-0.1 ppm). Smoking healthy control subjects had the highest levels of exhaled CO concentration among the groups (21.6+/-2.8 ppm, p < 0.001). To examine whether inhaling corticosteroids reduce exhaled CO concentration in a given asthmatic patient, 12 patients with symptomatic asthma who were being treated by inhaled beta2-agonists alone underwent measurements of exhaled CO concentration before and 4 wk after the initiation of inhaled corticosteroid treatment. All patients had reductions in exhaled CO concentration (p < 0.001) and eosinophil cell counts in sputum (p < 0.01) that were accompanied by an improvement in airway obstruction. Changes in exhaled CO concentration were significantly related to those in the eosinophil cell counts in sputum (p < 0.001). The present study shows an elevation of exhaled CO in asthmatic patients that decreases with corticosteroid therapy. Increases in the exhaled CO levels therefore may reflect inflammation in the asthmatic lung.
Recombinant factor Vila was used to treat 38 patients with acquired haemophilia participating in the Novoseven compassionate-use program. 19 were male, median age 59, range 2-89 years. The median pre-treatment anti-human (H) and anti-porcine (P) inhibitor titre was H 43 BU/ml (range 1-4500) and P 4.5 BU/ml (range 0-1600). Recombinant factor VIIa was used as first-line therapy for 14 bleeding episodes and as salvage-therapy for 60 episodes which failed to respond to blood-product therapy given for a median of four days (range 1-21 days) prior to treatment with rVIIa. Pre-rVIIa treatment was not reported for four episodes. The indications for treatment were 7 haemarthroses, 40 muscle haematomas, 20 urinary or GI haemorrhages and 3 surgical interventions. The median starting dose of rVIIa was 90.4 ug/kg (range 45-181). A median of 28 doses (range 1-541) were given per episode, over a median 3.9 days (range 0-43).
Efficacy was assessed clinically 8 and 24 h after the start of rVIIa and at the end of treatment. A good response was obtained in all 14 bleeds for which rVIIa was used as first-line therapy. The response after 24 h of rVIIa salvage-therapy for 60 bleeds was good in 75%, partial in 17% and poor in 8%. Efficacy was unreported in 4 cases. The median prothrombin time (PTT) shortened from 12 s (range 9.3-20) pre-treatment to 8.8 s (range 6-14) during treatment. The clinical response did not correlate with the dose of rVIIa used, the type of bleed or the degree of shortening of the PTT following rVIIa infusion.
Three patients died from haemorrhagic complications of acquired haemophilia. This mortality of 7.9% is lower than previously reported for this condition. Although one patient developed DIC during treatment with rVIIa, this was probably attributable to hypovolaemic shock, massive transfusion and the use of PCCs. This study demonstrates that rVIIa is a safe, useful and effective treatment for bleeding in patients with acquired haemophilia.
The incidence of collagenous and lymphocytic colitis is not well known. We sought to assess the incidence of collagenous and lymphocytic colitis in a well-defined population during a 5-yr study period.
From January 1, 1993, to December 31, 1997, all new patients diagnosed with collagenous or lymphocytic colitis living in the catchment area of the Hospital Mutua de Terrassa (Barcelona, Spain) were identified. Since 1993 all patients with chronic diarrhea were referred for a diagnostic colonoscopy. Multiple biopsy sampling of the entire colon was performed when appearance of the colonic mucosa was grossly normal.
Twenty-three cases of collagenous colitis and 37 of lymphocytic colitis were diagnosed. The female:male ratios were 4.75:1 and 2.7:1 for collagenous and lymphocytic colitis, respectively. The mean age at onset of symptoms was 53.4+/-3.2 (range, 29-82) yr for collagenous colitis, and 64.3+/-2.7 (range, 28-87) yr for lymphocytic colitis (p = 0.012). The mean annual incidence per 100,000 inhabitants based on the year of onset of symptoms was 1.1 (95% confidence interval [CI], 0.4-1.7) for collagenous colitis, and 3.1 (95% CI, 2.0-4.2) for lymphocytic colitis. A peak incidence was observed in older women in both diseases. A rate of microscopic colitis of 9.5 per 100 normal-looking colonoscopies performed in patients with chronic watery diarrhea was observed. Normal rectal biopsies were found in 43 % and 8% of patients with collagenous and lymphocytic colitis, respectively.
The incidence of lymphocytic colitis is three times higher than that of collagenous colitis. Microscopic colitis should be considered as a major possibility in the work-up of chronic diarrhea in older women.
Acquired haemophilia is a rare but life-threatening acquired bleeding diathesis caused by autoimmune depletion of factor VIII. This occurs most frequently in elderly patients who lack disease associations. Acquired haemophilia may also arise in association with SLE rheumatoid arthritis, Sjögren's syndrome, other autoimmune conditions, lymphoproliferative malignancy, pregnancy and as a drug reaction. Acquired haemophilia has an equal sex distribution. The aims of treatment are to eliminate the inhibitor by immunosuppression and to treat the bleeding, which is the most common cause of death in patients with acquired haemophilia. The inhibitor is abolished in up to 70% of patients using prednisolone and cyclophosphamide, although other immunosuppressive regimens may also be used. These include azathioprine, vincristine and other cytotoxic agents, high-dose immunoglobulin and cyclosporin A. Bleeding may be controlled using porcine factor VIII or recombinant factor VIIa, although human factor VIII and prothrombin complex concentrates also have a limited role as haemostatic agents in this condition.
No data are available on gender- and age-specific incidences for bullous pemphigoid (BP). The aim of this study was to calculate incidences for different gender- and age-strata and to assess risk differences between these strata in BP. A retrospective population-based cohort was recruited from all patients diagnosed with BP in 2 well-defined regions of Germany. The average population number was 1.7 million, and the observation period was 9 years (1989-1997). Incidences were calculated as newly diagnosed cases for a population of 1 million per year. Confidence intervals (CI) were estimated based on a Poisson distribution. For evaluation of risk between different age and gender strata a Poisson regression analysis was used. The highest incidence was calculated for individuals older than 90 years, with 398 (CI: 360, 439) new cases of BP per 1 million residents for men, and 87 (CI: 70, 108) new cases per 1 million residents for women. Risk (95% CI) was 1.9 (1.3, 2.9) fold higher in men than in women. In addition, the risk for BP was increased for patients above the age of 60 years. The highest risk was found for patients older than 90 years. For this age group, the risk was 297 (CI: 107, 826) fold higher than in patients 60 years of age and younger. Men are affected by BP almost twice as often as women. The risk for BP increases rapidly beyond the age of 60 years. Because the structure of the European population is shifting towards the aged, more people are expected to suffer from BP in the coming decades.
In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis.
To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis.
Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the (75)Se-homocholic acid taurine ((75)SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the (75)SeHCAT test.
Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The (75)SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with (75)SeHCAT values 0.5-9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal (75)SeHCAT tests.
Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.
More than 50% of the elderly population has not received pneumococcal vaccination. Uncertainty regarding the benefits of immunization, particularly for noninvasive disease, may contribute to the underuse of pneumococcal vaccine.
To assess the health and economic benefits associated with pneumococcal vaccination.
We conducted a 2-year retrospective cohort study among all elderly members of a staff-model managed care organization who had a baseline diagnosis of chronic lung disease. The study outcomes were assessed over 2 years, from November 15, 1993, through November 14, 1995, and included hospitalizations for pneumonia and influenza, death, and hospitalization costs. Using administrative data, we compared these outcomes for vaccinated and unvaccinated subjects using multivariate models to control for subjects' baseline demographic and health characteristics. The additive benefits of combined influenza and pneumococcal vaccination were also assessed for the 2 influenza seasons included in the study.
There were 1898 subjects. Pneumococcal vaccination was associated with significantly lower risks for pneumonia hospitalizations (adjusted risk ratio [RR], 0.57; 95% confidence interval [CI], 0.38-0.84; P=.005) and for death (adjusted RR, 0.71; 95% CI, 0.56-0.91; P = .008). For the control outcome of all nonpneumonia hospitalizations, rates did not differ significantly between the 2 groups (adjusted RR, 0.91; 95% CI, 0.77-1.07; P= .24). During the influenza seasons included in the study, the benefits of pneumococcal and influenza vaccinations were additive, with an adjusted RR of 0.28 (95% CI, 0.14-0.58; P<.001) for the number of hospitalizations for pneumonia and influenza among persons who had received both vaccinations compared with those who had received neither and an adjusted odds ratio of 0.18 (95% CI, 0.11-0.31; P<.001) for death. Over the 2-year outcome period, pneumococcal vaccination was also associated with direct medical care cost savings.
Pneumococcal vaccination of elderly persons with chronic lung disease was associated with fewer hospitalizations for pneumonia, fewer deaths, and direct medical care cost savings.
We present a case that suggests a relationship between primary biliary cirrhosis and myasthenia gravis. A 43-year-old Japanese woman was admitted to the Nagoya City University Medical School, First Department of Internal Medicine with abnormal liver function in August 1991. She had had ptosis of the right eye since 1990. She had not been treated for liver disease. Ptosis of the right eye and hepatomegaly were present. Serum laboratory examinations revealed elevated biliary enzymes and IgM levels; tests were positive for antimitochondrial antibody and antiacetylcholine antibody. Liver histology revealed chronic non-suppurative destructive cholangitis and led to a diagnosis of primary biliary cirrhosis. The tensilon test was positive. Electromyography with repetitive motor nerve stimulation revealed a neuromuscular junction defect; i.e., the primary characteristic of myasthenia gravis. The patient was diagnosed with myasthenia gravis. Although the development of myasthenia gravis has previously been reported in patients with primary biliary cirrhosis during D-penicillamine administration, this is a very rare case of the coexistence of both diseases before such treatment.
Bullous pemphigoid (BP) occurs in many patients with multiple sclerosis. Isolated cases of BP in patients with other neurological disorders further support a pathogenic association between cutaneous and neurological diseases. Any description of BP in patients with amyotrophic lateral sclerosis is lacking.
We studied a French population of 168 patients with typical amyotrophic lateral sclerosis. Among these, 3 had clinical and histological features of BP. The mean age of the patients was 54 years. None was known to have autoimmune disorders. Results of immunoblot analysis disclosed both anti-BP antigen 1 and anti-BP antigen 2 antibodies.
Bullous pemphigoid seems to be unexpectedly associated with amyotrophic lateral sclerosis. On the basis of the cases presented herein, we discuss the epidemiological significance of the association and the possible interrelation between BP antigen 1 and neurofilaments in the pathogenesis of both disorders.
To investigate the pathogenesis of proximal diabetic neuropathy (PDN) with nerve and muscle biopsies.
Recent evidence suggests that nerve ischemia secondary to immune-mediated vasculopathy rather than diabetic microangiopathy may be responsible for PDN.Method:- Fifteen patients with PDN and two diabetic controls underwent nerve and muscle biopsy and clinical, electrophysiologic, and laboratory evaluation. There were eight men and seven women between 49 and 79 years of age with type II diabetes. All had progressive, painful, asymmetric, proximal weakness with duration of 5 weeks to 12 months. None had evidence of systemic autoimmune disorder.
Four patients showed the distinctive findings of polymorphonuclear small-vessel vasculitis affecting epineurial vessels with transmural infiltration of postcapillary venules with polymorphonuclear leukocytes. Immunoglobulin M (IgM) deposits were found along the endothelium and intramurally in affected vessels. IgM staining was seen in the subperineurial space and in the endoneurium. Activated complement deposition was seen along endothelium of small vessels. Three of these four patients were evaluated within 6 seeks of onset of PDN, and the fourth patient during acute flare of PDN 6 months after the initial onset. Six patients showed "perivasculitis" with mononuclear cell infiltrates around small epineurial vessels without vasculitis (fibrinoid necrosis or transmural inflammation). One patient showed recanalized vessels with transmural lymphocytes without fibrinoid necrosis, possibly suggesting healed vasculitis.
These distinctive pathologic findings support that proximal diabetic neuropathy has an immune-mediated inflammatory basis and suggest that polymorphonuclear vasculitis with immune complex and complement deposition may be the primary event in the acute phase of proximal diabetic neuropathy.