The diagnostic criteria for microscopic colitis are: a)Chronic or intermittent non-bloody watery diarrhea b)Colonic mucosa assessed by colonoscopy macroscopically normal or near normal c)Characteristic histopathological findings. In our case, the patient presents findings compatible with collagenous colitis (band of collagen underlying the epithelium greater than 10 microns) and lymphocytic (more than 20 intraepithelial lymphocytes). The treatment of this pathology is topical corticosteroids with low oral bioavailability (mainly budesonide). Olmesartan enteropathy produces a picture similar to celiac disease and is characterized by duodenal biopsy with villous atrophy, mucosal inflammation with increased intraepithelial lymphocytes and cryptitis. In this case a normal duodenal biopsy is described, but it would be interesting to keep the concept for future examinations.

A 79-year-old hypertensive woman on treatment with olmesartan comes for consultation for watery diarrhea of 4 to 6 stools per day for the past two months. Three months ago she was treated with nonsteroidal anti-inflammatory drugs for 3 weeks for lumbosciatica. Gastroscopy and colonoscopy were performed, both without macroscopic alterations. Duodenal biopsies were normal, while colon biopsies showed a chronic inflammatory infiltrate of the lamina propria with an irregular band of collagen immediately below the mucosal surface epithelium with a thickness greater than 10 mm and a number of intraepithelial lymphocytes >20 per 100 epithelial cells. Which is the most likely diagnosis?

[Are lymphocytic and collagenous colitis two forms of a single disease? Arguments taken from a biopsy quantitative study].

Collagenous colitis and lymphocytic colitis are defined by a clinicopathologic syndrome with chronic watery diarrhea, microscopic lesions of colonic biopsies, and normal barium enema and colonoscopy. A histopathological study was performed on multiple colorectal biopsies to compare 12 cases of collagenous colitis (defined by a subepithelial collagen thicker than 10 microns) and 7 cases of lymphocytic colitis (defined by a number of intraepithelial lymphocytes more than 20 per 100 epithelial cells at least in one biopsied site). The study included a semiquantitative analysis of inflammatory infiltrate in the lamina propria, crypts distortion and epithelial detachment. The number of intraepithelial lymphocytes per 100 epithelial cells was determined in surface epithelium and crypts. The subepithelial collagen thickening was studied by computerised morphometry. The intraepithelial lymphocytes, villous atrophy and thickness of the subepithelial collagen were also determined in gastric and duodenal biopsies. In collagenous colitis, the subepithelial collagenous thickness ranged from 10 to 40 microns in the colon (median 20.99 microns). In 4 cases of collagenous colitis, no thickening of the collagen plate was seen in the rectum. We found constant epithelial detachment and mucosal distortion. In lymphocytic colitis, the thickness of the subepithelial collagen ranged from 6 to 10 microns in 4 cases and was less than 6 microns in 3 cases (median 6.24 microns). The median number of intraepithelial lymphocytes in surface epithelium was 22.35 (range 18.2 to 40) in lymphocytic colitis versus 12.22 (range 4.6 to 24.4) in collagenous colitis. In conclusion, we observed an overlap of both the collagenous plate thickness and the number of intraepithelial lymphocytes in collagenous colitis and lymphocytic colitis. This result favours a unified histogenesis for these two entities.

Chronic use of non-steroidal anti-inflammatory drugs does not alter colonic mucosa of patients without diarrhoea.

Several types of colitis can be NSAID-induced, but whether chronic use of NSAIDs alters colonic mucosa in patients without diarrhoea is not known. Biopsy specimens of rectal mucosa were taken in six patients with rheumatoid arthritis without diarrhoea receiving NSAIDs (group 1, n=6). Patients with rheumatoid arthritis without diarrhoea not receiving NSAIDs (group 2, n=9), and patients undergoing surveillance colonoscopy (group 3, n=23) served as controls. In all patients from the three study groups, intraepithelial lymphocyte count and apoptotic cell count were assessed, and sub-epithelial collagen band thickness was measured. Leucocyte population of lamina propria was evaluated semi-quantitatively. HLA-DR and CD25 expression of mucosal cells was appreciated by immunohistochemistry. Intraepithelial lymphocyte count was in the normal range in all three group patients, and not statistically different between groups. Apoptotic epithelial cell count was not different between groups. Sub-epithelial collagen band thickness was normal in all the patients. No patient had a marked infiltration of lamina propria by leucocytes, and HLA-DR and CD25 were normally expressed in all patients. These results from a small sample of patients suggest that patients without diarrhoea receiving NSAIDs on a long-term basis do not develop microscopic or inflammatory colitis.

Prevalence of microscopic colitis in patients with diarrhea of unknown etiology in Turkey.

To investigate the prevalence and demography of microscopic colitis in patients with diarrhea of unknown etiology and normal colonoscopy in Turkey. Between March, 1998 to July, 2005, 129 patients with chronic non-bloody diarrhea of unexplained etiology who had undergone full colonoscopy with no obvious abnormalities were included in the study. Two biopsies were obtained from all colonic segments and terminal ileum for diagnosis of microscopic colitis. On histopathologic examination, criteria for lymphocytic colitis (intraepithelial lymphocyte >or= 20 per 100 intercryptal epithelial cells, change in surface epithelium, mononuclear infiltration of the lamina propria) and collagenous colitis (subepithelial collagen band thickness >or= 10 microm) were explored. Lymphocytic colitis was diagnosed in 12 (9%) patients (Female/Male: 7/5, mean age: 45 year, range: 27-63) and collagenous colitis was diagnosed in only 3 (2.5%) patients (all female, mean age: 60 years, range: 54-65). Biopsy of Turkish patients with the diagnosis of chronic non-bloody diarrhea of unexplained etiology and normal colonoscopic findings will reveal microscopic colitis in approximately 10% of the patients. Lymphocytic colitis is 4 times more frequent than collagenous colitis in these patients.

[Functional diarrheas are not, in most cases, minor clinical forms of lymphocytic or collagenous colitis].

The aim of the study was to test the hypothesis that some patients with functional diarrhea could actually suffer from a mild clinical pattern of collagenous or lymphocytic colitis. Twenty consecutive patients with chronic diarrhea were included in the study if the colonic mucosa appeared normal during colonoscopy. From multiple colonic biopsies were established a conventional histological diagnosis and a quantitative histological diagnosis. This latter diagnosis was based on the semiquantitative evaluation of epithelial morphological alterations and lamina propria monocellular infiltration, and on the determination of both intraepithelial lymphocyte count and subepithelial collagen layer thickness. Multiple colonic biopsies from 12 control patients without diarrhea were analyzed according to the same protocol. Among the 20 patients with diarrhea, the quantitative diagnosis of collagenous colitis was made in 3 patients (thickness of the collagen band between 11 and 26 microns) and the diagnosis of lymphocytic colitis in one (21% of intraepithelial lymphocytes). The percentage of intraepithelial lymphocytes did not differ between the 16 remaining patients and the controls (12 +/- 5% and 9 +/- 4%, respectively). Similarly, the score of surface epithelial damage and the score of lamina propria infiltration in patients with diarrhea (1.2 +/- 1.0 et 1.7 +/- 1.5) were not different from the values in the control group (1.3 +/- 1.3 et 1.5 +/- 1.2). The mean fecal weight in patients with diarrhea but without colitis was 161 +/- 130 g/d. All the values of fecal weight were below 300 g/d, except in one patient with a past history of truncular vagotomy. These results suggest that most of the patients with functional diarrhea do not suffer from mild clinical patterns of collagenous or lymphocytic colitis.

Microscopic colitis

Diagnosis Colonoscopic appearances are normal or near normal. As the changes are often patchy, an examination limited to the rectum may miss cases of microscopic colitis, and so a full colonoscopy is necessary. Multiple colonic biopsies are taken in order to make the diagnosis. Histological features of colonic biopsies indicating microscopic colitis are: greater than 20 intraepithelial lymphocytes per 100 epithelial cells and, additionally, 10-20 μm of a thickened subepithelial collagen band in collagenous colitis. Inflammation of the lamina propria, with mainly mononuclear cells, may be observed in collagenous colitis.

[Microscopic colitis: collagenous colitis and lymphocytic colitis].

Microscopic colitis is currently classified as a chronic inflammatory bowel disorder and encompasses two entities: lymphocytic colitis and collagenous colitis. Patients with microscopic colitis present with a well-tolerated chronic watery diarrhea, sometimes with abdominal pain. Colonoscopy is normal. Diagnosis of microscopic colitis is established by histologic examination of colonic biopsies, showing a thickened subsurface collagen band higher than 10 microm in collagenous colitis, and an increased number of surface intra-epithelial lymphocytes higher than 20 lymphocytes per 100 epithelial cells in lymphocytic colitis. Causes of microscopic colitis are still unknown, although a drug-induced etiology is found in some cases. Patients are usually treated with budesonide but recurrences are frequent.

Microscopic colitis: a narrative review with clinical approach.

Microscopic colitis (MC) is diagnosed in presence of microscopic alterations of colonic mucosa, in patients without macroscopic lesions who referred for chronic diarrhea. The two types of MC are lymphocytic colitis (LC) and collagenous colitis (CC), but it is unclear whether these are the different expression of one unique disease or if they are distinct conditions. Today, although MC represents a consistent health problem, being responsible for a large part of gastroenterological consultations for diarrhea, it remains often underestimated. The detailed pathogenesis of MC has not been determined yet. Probably, it is the result of an interaction between individual, environmental and genetic factors. The most relevant risk factor for the development of MC is the use of certain drugs (such as non-steroidal anti-inflammatory drugs [NSAIDs], proton pump inhibitors [PPIs], selective serotonin reuptake inhibitors, beta-blockers, statins). Smoking is another relevant factor reported as associated with the development of MC. Diagnosis needs the execution of a colonoscopy in patients complaining about chronic diarrhea and abdominal pain. The crucial role is played by histology: MC is characterized by the presence of colonic mucosal lymphocytic infiltrate, with intraepithelial lymphocytes ≥20 per 100 enteric surface cells, in CC there is a typical subepithelial collagen layer, whose thickness is ≥10 μm. We carried out a review of the current literature to rule out what is new on epidemiology, diagnosis and therapy of MC.

Lymphocytic colitis

Lymphocytic colitis is a subtype of microscopic colitis, a condition characterized by chronic non-bloody watery diarrhea. Causes No definite cause has been determined. The peak incidence of lymphocytic colitis is in persons over age 50; the disease affects women and men equally. Some reports have implicated long-term usage of NSAIDs, proton pump inhibitors, and selective serotonin reuptake inhibitors, and other drugs. Associations with other autoimmune disorders suggests that overactive immune responses occur. Diagnosis The colonoscopy is normal but histology of the mucosal biopsy reveals an accumulation of lymphocytes in the colonic epithelium and connective tissue (lamina propria). Collagenous colitis shares this feature but additionally shows a distinctive thickening of the subepithelial collagen table.

[Enteropathy due to olmesartan].

The olmesartan is a selective antagonist of angiotensin II indicated for the treatment of essential hypertension. We report the case of a gastrointestinal involvement with duodenal villous atrophy and lymphocytic infiltrate duodenal epithelial and colonic secondary to the olmesartan taking with test of positive reintroduction. The patient had chronic diarrhea with weight loss of 10kg occurred 1 month after the passage of 20 to 40mg/day olmesartan took 3 years. A rectosigmoidoscopy highlighted some puncture slightly erythematous areas. The responsibility of olmesartan was suspected and the drug was stopped. The evolution was rapidly favorable with disappearance of diarrhea 4 8hours later. Two days after the patient took the drug on its own initiative. Sigmoid biopsies showed an inflammatory infiltrate rich in lymphocytes. Gastroscopy showed erosive esophagitis and duodenal biopsies showed chronic duodenitis with epithelial lymphocytosis and subtotal villous atrophy. The reintroduction has led to the immediate resumption of diarrhea. olmetec was finalized. Diarrhea has not returned since. A colonoscopy performed 6 weeks after discharge was normal. Knowledge of the bowel olmesartan is recent and based almost solely on the description of 22 cases observed at the Mayo Clinic with patients, as in our case, have similar symptoms and lesions. We stress about a publication an isolated case the possibility of less severe cases with histological abnormalities without clinical translation.

[Enteropathy due to olmesartan].

The olmesartan is a selective antagonist of angiotensin II indicated for the treatment of essential hypertension. We report the case of a gastrointestinal involvement with duodenal villous atrophy and lymphocytic infiltrate duodenal epithelial and colonic secondary to the olmesartan taking with test of positive reintroduction. The patient had chronic diarrhea with weight loss of 10kg occurring one month after the passage of 20 to 40mg/day olmesartan took three years. A rectosigmoidoscopy highlighted some puncture slightly erythematous areas. The responsibility of olmesartan was suspected and the drug was stopped. The evolution was rapidly favorable with disappearance of diarrhea 48hours later. Two days after the patient took the drug on its own initiative. Sigmoid biopsies showed an inflammatory infiltrate rich in lymphocytes. Gastroscopy showed erosive esophagitis and duodenal biopsies showed chronic duodenitis with epithelial lymphocytosis and subtotal villous atrophy. The reintroduction has led to the immediate resumption of diarrhea. Olmesartan was finalized. Diarrhea has not returned since. A colonoscopy performed six weeks after discharge was normal. Knowledge of the bowel olmesartan is recent and based almost solely on the description of 22 cases observed at the Mayo Clinic with patients, as in our case, have similar symptoms and lesions. We stress, about a publication of an isolated case, the possibility of less severe cases with histological abnormalities without clinical translation.

Microscopic colitis

Pathology Microscopic colitis is characterized by an increase in inflammatory cells, particularly lymphocytes, in colonic biopsies with an otherwise normal appearance and architecture of the colon. Inflammatory cells are increased both in the surface epithelium ("intraepithelial lymphocytes") and in the lamina propria. The key feature is more than 20 intra-epithelial lymphocytes per 100 epithelial cells. These are the principal features of lymphocytic colitis. An additional distinguishing feature of collagenous colitis is a thickened subepithelial collagen layer, which may be up to 30 micrometres thick, that occurs in addition to the features found in lymphocytic colitis. The fact that the two types of microscopic colitis share many features including epidemiology, risk factors and, response to therapy has led to the suggestion that they are actually subtypes of the same disease.

Microscopic colitis in patients with mild duodenal damage: A new clinical and pathological entity ("lymphocytic enterocolitis")?

To evaluate the potential association between mild duodenal damage and microscopic colitis (MC). We retrospectively included 105 consecutive patients with type I Marsh-Oberhuber duodenal damage and negativity for immunoglobulin A anti-endomysium and anti-tissue transglutaminase. The following parameters were analyzed: Sex, age at execution of esophagogastroduodenoscopy, duodenal damage, and number of intraepithelial lymphocytes at biopsies, prevalence of <iHelicobacter pylori</i infection, age at execution of colonoscopy, macroscopic and microscopic features of colonoscopy, family history of gastrointestinal and autoimmune diseases, smoking habits, biochemical parameters of inflammation and autoimmunity, use of proton pump inhibitors or nonsteroidal anti-inflammatory drugs, adverse reactions to drugs or foods, pathologies known to be associated with celiac disease or MC, living on a gluten-free diet or on a gluten-low diet for at least 1 mo. Colonoscopy was performed in 59 patients, but only in 48 of them biopsies were taken in the entire colon. Considering the latter cohort, the diagnosis of MC was met in 25 (52.1%) patients while in 18 patients other pathologic findings were reported: 13 (27%) cases of nonspecific inflammatory bowel disease, 2 (4.2%) cases of Crohn's disease, 2 (4.2%) cases of eosinophilic gastroenteritis, and 1 (2.1%) case of autoimmune enteritis. Five (10.4%) patients had a normal colonoscopic result. Matching the groups by age, and considering only patients who underwent colonoscopy (42.7 ± 15.5 years) <ivs</i those who did not undergo colonoscopy (36.9 ± 10.6 years), a statistical difference was found (<iP</i = 0.039). Focusing on symptoms, diarrhea was statistically more prevalent in MC group than in patients who did not undergo colonoscopy (<iP</i = 0.03). Mild duodenal damage is associated with MC in more than half of the cases. This association supports the hypothesis of a link between these two entities.

Endoscopic and histopathological evaluation of collagenous colitis.

Collagenous colitis (CC) is a well-known cause of chronic non-bloody diarrhea, especially in elderly women. CC is characterized histopathologically by an increase in the thickness of the subepithelial collagen layer to at least 10 μm, epithelial damage, and chronic inflammation of the lamina propria. Generally, the colonic mucosa in CC is macroscopically normal, although minor, non-specific abnormalities may be found. Due to the recent advancement of endoscopic and diagnostic technologies, however, microscopic mucosal abnormalities and specific longitudinal linear lacerations of the mucosa characteristic of CC have been identified. The association of CC with non-steroidal anti-inflammatory drugs and proton pump inhibitors has also been reported. Since definitive diagnosis of CC has to rely on pathologically documented collagen bands and mononuclear infiltration, the efficiency and precision of colonic biopsy need to be improved. Of the 29 CC patients that we have encountered at our institution, it was in 15 of 29 cases that the endoscopic finding that we performed a biopsy on was apparent. Our comparison of the endoscopic and histopathological findings of CC in the 15 patients showed that the mucosa frequently appeared coarse and nodular on the surface of the mucosa, which was also significantly thicker in collagen bands, demonstrating a strong correlation between collagen band formation and CC. Also, the coarse and nodular surface of the mucosa was most frequently seen affecting the proximal colon. The results suggest that endoscopic observation and biopsy of the proximal colon, where a coarse and nodular surface of the mucosa is often found, may be useful for confirmation of the diagnosis in patients with suspected CC.

[Histopathology of microscopic colitis].

Microscopic colitis (MC) is recognized to be a common cause of chronic, non-bloody diarrhea with rising incidence in the last decade. The diagnosis can only be made by histology and the specific histological findings define two subtypes of MC: lymphocytic (LC) or collagenous colitis (CC). The key histological feature of LC is an increased number of surface intraepithelial lymphocytes (IEL). In the literature, >20 IELs/100 epithelial cells are required to warrant the diagnosis of LC. IELs are mostly cytotoxic CD8+ T-lymphocytes. The key histological criterion for CC is a continuous subepithelial fibrous band underneath the surface epithelium (>10 µm). Other hallmarks of CC are chronic mucosal inflammation, and the collagen band can contain entrapped capillaries, red blood cells, and inflammatory cells. Damaged epithelial cells appear flattened, mucin depleted, and irregularly oriented. Focally, small strips of surface epithelium may lift off from their basement membrane. In both subtypes of MC, the lamina propria shows increased numbers of plasma cells and lymphocytes with loss of the normal gradient, even eosinophilic and neutrophilic granulocytes may be present. But these histological features alone do not warrant the diagnosis of MC even though they may be responsible for the clinical symptoms. The term MCi (MC incomplete) is suggested for the subgroup of patients with diarrhea and an increase in cellular infiltrate in the colonic lamina propria and either an abnormal collagenous layer and/or intraepithelial lymphocytes coming but not fulfilling the criteria for CC or LC.

Collagenous and lymphocytic colitis.

Collagenous and lymphocytic colitis have been recognized as chronic intestinal inflammatory disorders causing watery diarrhea, which have been recognized in the past three to two decades, respectively. Collagenous colitis is primarily a disorder of middle-aged women and is characterized on biopsy by increased subepithelial collagen as well as increased inflammatory cells in the lamina propria and increased intraepithelial lymphocytes. Key to the correct diagnosis in this condition is recognizing that there are two words in this diagnostic entity, and colitis is, by definition, present. Focusing solely on the collagen band can result in both over- and underdiagnosis. Newer therapeutic options are available in this condition, and patients are now frequently being treated either with budesonide or with high dose bismuth preparations. Whereas collagenous colitis is a tightly coherent clinical pathologic entity, lymphocytic colitis has a more varied clinical picture. Lymphocytic colitis is also seen in middle-aged patients but has a more equal female-to-male ratio. Lymphocytic colitis is defined by increased intraepithelial lymphocytes, with the median being 30 lymphocytes per 100 epithelial cells. There are also an increase in inflammatory cells in the lamina propria, but the increase may be milder than in collagenous colitis and there are usually minimal eosinophils. Although numerous studies have described lymphocytic colitis causing a chronic diarrhea, more recent studies suggest that patients may have a single attack in approximately 60% of cases. Although most cases of lymphocytic colitis are idiopathic, there is a clear association with multiple drugs, celiac disease, and there may be an infectious trigger. Approximately 10% of lymphocytic colitis patients have a positive family history of some type of inflammatory intestinal disease, including ulcerative colitis, Crohn's disease, collagenous colitis, and celiac disease. Therapy in lymphocytic colitis is less well studied, but the same medications are used with success, including budesonide and high dose bismuth.

Histological disease activity in patients with microscopic colitis is not related to clinical disease activity or long-term prognosis.

Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course. To identify possible histological predictors of course of disease. Sixty patients from the European prospective MC registry (PRO-MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1-year follow-up. Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1-year follow-up. Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.

Microscopic colitis in patients presenting with chronic diarrhea.

To investigate the prevalence of microscopic colitis among patients presenting with chronic watery diarrhea. Colonic biopsies from 400 patients presenting with chronic watery diarrhea and other symptoms pertaining to lower gastrointestinal tract were studied. After a detailed clinical history and thorough physical examination full length colonoscopy was done using flexible colonoscope. Colonic biopsies were taken from abnormal and normal areas. Three to five micron thick sections were cut and stained with hematoxylin and eosin and Masson's trichrome stain to highlight sub epithelial collagen. Fifteen out of 400 (3.7%) colonic biopsies from patients presenting with chronic diarrhea had evidence of microscopic colitis. Five out of fifteen biopsies (33%) were diagnosed as collagenous colitis, 10 biopsies (67%) had evidence of lymphocytic colitis; 14/400(3.5%) histologically normal biopsies were taken as controls to compare various demographic and risk factors. Ten out of 15 patients (67%) were clinically diagnosed as irritable bowel syndrome. In the remaining five an infective etiology was suspected. On colonoscopy12/15 (80%) had no abnormality and 3/15 (20%) had mild hyperemia. A possibility of microscopic colitis should be considered while examining colonoscopic biopsy of a patient with chronic watery diarrhea and normal colonoscopy to avoid the misdiagnosis that may affect the treatment of patients.

Undiagnosed microscopic colitis: a hidden cause of chronic diarrhoea and a frequently missed treatment opportunity.

Microscopic colitis (MC) is a treatable cause of chronic, non-bloody, watery diarrhoea, but physicians (particularly in primary care) are less familiar with MC than with other causes of chronic diarrhoea. The colon in patients with MC is usually macroscopically normal. MC can only be diagnosed by histological examination of colonic biopsies (subepithelial collagen band >10 µm (collagenous colitis) or >20 intraepithelial lymphocytes per 100 epithelial cells (lymphocytic colitis), both with lamina propria inflammation). The UK National Health Service exerts downward pressure to minimise colonoscopy referrals. Furthermore, biopsies are often not taken according to guidelines. These factors work against MC diagnosis. In this review, we note the high incidence of MC (comparable to ulcerative colitis and Crohn's disease) and its symptomatic overlap with irritable bowel syndrome. We also highlight problems with the recommendation by National Health Service/National Institute for Health and Care Excellence guidelines for inflammatory bowel diseases that colonoscopy referrals should be based on a faecal calprotectin level of ≥100 µg/g. Faecal calprotectin is <100 µg/g in over half of individuals with active MC, building into the system a propensity to misdiagnose MC as irritable bowel syndrome. This raises important questions-how many patients with MC have already been misdiagnosed, and how do we address this silent burden? Clarity is needed around pathways for MC management; MC is poorly acknowledged by the UK healthcare system and it is unlikely that best practices are being followed adequately. There is an opportunity to identify and treat patients with MC more effectively.

Microscopic colitis

Microscopic colitis refers to two related medical conditions which cause diarrhea: collagenous colitis and lymphocytic colitis. Both conditions are characterized by the presence of chronic non-bloody watery diarrhea, normal appearances on colonoscopy and characteristic histopathology findings of inflammatory cells. Signs and symptoms The main symptom is persistent non-bloody watery diarrhea, which may be profuse. People may also experience abdominal pain, fecal incontinence, and unintentional weight loss. Microscopic colitis is the diagnosis in around 10% of cases investigated for chronic non-bloody diarrhea.

[Chronic diarrhea due to lymphocytic colitis treated with piroxicam beta cyclodextrin].

Lymphocytic colitis is a chronic diarrhea syndrome with no endoscopically detectable anomaly and histological colonic lesions. A 52-year-old woman was hospitalized for chronic diarrhea. She experienced 10 to 30 liquid bowel movements per day. Symptoms had begun 8 days after taking piroxicam fl-cyclodextrin. Intraepithelial cell counts on rectum and colon endoscopic biopsies showed more than 20% lymphocytes, giving the diagnosis of lymphocytic colitis. The patient was given 5ASA 3 g/24 h. Symptoms regressed in less than one week. Lymphocytic colitis is uncommon. The cause remains unknown but a secondary autoimmune mechanism triggered by drugs has been suggested. This case would implicate nonsteroidal antiinflammatory drugs. Certain authors have demonstrated that they can be involved in the development of collagen colitis.

Microscopic colitis in children with chronic diarrhea.

The aim of the present study was to study microscopic colitis (MC) in children with special reference to its role in chronic diarrhea and changes in mucosal biopsies. A total of 100 consecutive children ages 3 to 12 years, with nonbloody diarrhea (passage of ≥3 loose stools per day) of >12 weeks' duration were screened and 26 were enrolled in the study in which no specific etiology could be found and colonoscopy did not reveal any mucosal abnormality. Colonic biopsies were evaluated for the presence of lymphocytic colitis or collagenous colitis and those with the characteristic changes were defined to have MC (group A). Colonic biopsies from patients with MC were compared with biopsies from patients with chronic diarrhea but no evidence of MC (group B). One hundred children ages 3 to 12 years with bleeding per rectum were screened and colonic biopsies from 45 patients (group C) who had colonic mucosal changes but no vascular or polyp lesion were compared with patients with MC. Of the 26 patients with chronic diarrhea, MC was found in 5 (3 lymphocytic colitis and 2 collagenous colitis). Significantly higher polymorphonuclear infiltration was seen in group A as compared with group B (13.8 [5.4-20.6] vs 7.2 [0-19.6]; P = 0.03) or group C (13.8 [5.4-20.6] vs 4 [0-13.4]; P = 0.007). Intraepithelial lymphocytes (12 [4-32] vs 4 [0-24]; P = 0.008) and basement membrane thickening (3.5 [2.9-10.6] vs 2.5 [1.6-5.86]; P = 0.008) were also significantly higher in group A as compared with group C. MC was found to be present in children with nonbloody chronic diarrhea in children. Further multicentric studies may provide adequate data on its prevalence.

Suspicion of microscopic colitis raised by sonographic examination.

This report describes the case of a 57-year-old woman who was incidentally identified as having lymphocytic colitis after she underwent routine transabdominal sonographic examination. She initially reported having no irregularities in her bowel movements. Sonography revealed the following nonspecific findings: watery stool in the entire colon, slight thickening of the hypoechoic mucosal layer and moderate thickening of the hyperechoic submucosal layer of the colon, and no pathologic findings in the small intestine. On additional questioning, the patient said that she had had watery diarrhea for the last 10 years, with as many as 10 bowel movements daily. Endoscopic examination and biopsy were performed. Histopathologic examination of biopsy specimens showed lymphocytic infiltration of the mucosa and some collagen deposits, consistent with a diagnosis of lymphocytic colitis. Treatment was begun with loperamide, sulfasalazine, and budesonide. Within 3 weeks of the start of treatment, the number of bowel movements decreased to 1-2 daily. Follow-up sonography at that time revealed normalization of the bowel contents and disappearance of the thickened submucosal layer of the colon. Nonspecific sonographic findings like those in this case lead to the need to rule out various diseases through further appropriate evaluations to identify the correct diagnosis.

Intraepithelial and Lamina Propria Lymphocytes Do Not Correlate With Symptoms or Exposures in Microscopic Colitis.

Microscopic colitis, a common cause of diarrhea, is characterized by a largely normal appearance of the mucosa but increased numbers of lymphocytes in the epithelium and lamina propria on microscopy. We sought to determine whether T-cell percentage was associated with exposures or symptoms. We conducted a case-control study that enrolled patients referred for colonoscopy for diarrhea. Patients were classified as microscopic colitis cases or controls by an experienced pathologist. Participants provided information on symptoms and exposures during a telephone or internet survey. Research biopsies from the ascending colon and descending colon were examined using immunofluorescence stains for CD3, CD8, and FOXP3 to determine percent T cells per total epithelial or lamina propria cells. Digital images were analyzed by regions of interest using Tissue Studio. There were 97 microscopic colitis cases and 165 diarrhea controls. There was no association between demographic factors and percentage of intraepithelial or lamina propria T cells. In cases, the mean percent T cells were similar in the right colon and left colon. There was no association between mean percent T cells and stool frequency or consistency. There was no association with irritable bowel syndrome, abdominal pain, or medications purported to cause microscopic colitis. The lack of association between the density of T cells and medications raises further doubts about their role in disease etiology. Loose and frequent stools in patients with microscopic colitis are not correlated with T-cell density.

Collagenous ileitis: a study of 13 cases.

Collagenous ileitis (CI), characterized by subepithelial collagen deposition in the terminal ileum, is an uncommon condition. The few cases reported to date have been associated with collagenous colitis (CC) or lymphocytic colitis. Thirteen cases of CI retrieved over a 9-year period were retrospectively studied. There were 7 female and 6 male patients, with an age range of 39 to 72 years (mean, 64 y). Two groups were identified: (1) CI associated with collagenous or lymphocytic disease elsewhere in the gastrointestinal tract and (2) CI as an isolated process. Diarrhea was the presenting symptom in 11 cases. Most patients had no regular medication use. Subepithelial collagen thickness ranged from 15 to 100 μm (mean, 32 μm) and involved 5% to 80% of the subepithelial region of the submitted biopsies. Six cases had >25 intraepithelial lymphocytes (IELs)/100 epithelial cells, and villous blunting was observed in 11 cases. Chronic inflammation of the lamina propria was present in 9 cases, and focal neutrophil infiltration was identified in 3 cases. In biopsies taken from other sites, 7 of 13 colonic biopsies showed CC, 4 of 9 gastric biopsies showed collagenous gastritis, and 2 of 10 duodenal biopsies were abnormal with collagenous sprue (n=1) and partial villous atrophy and increased IELs (n=1) (both celiac disease related). Resolution of the subepithelial collagen deposition was found in the 1 case in which follow-up of terminal ileal biopsies were taken. There was partial or complete resolution of symptoms in 6 of 9 patients for whom follow-up information was available.

[Microscopic colitis].

A 38-year old woman is admitted in the gastroenterology unit for a disabling episode of watery diarrhoea, not bloody and refractory to anti-diarrheic drugs. Different diagnostic exams remain negatives, with the exception of colic biopsies who disclose a lymphocytic colitis, one of the forms of the microscopic colitis entity. Microscopic colitis is an anatomo-clinic syndrome characterized by the presence of histological abnormalities on colic biopsies amongst patients suffering from chronic watery diarrhoea without endoscopic anomalies. Two clinical entities are today well known: collagenous colitis is characterized by a thickening of the sub-epithelial collagen band of the colon; lymphocytic colitis is defined as an increased level of lymphocytic cells, more than 20%, in the epithelial surface of colorectal mucosa. Inflammatory lesions of the chorion and alterations of the epithelial surface are seen in the two types of colitis. Their etiology remains unknown. It could be due to inflammatory lesions from autoimmune origin, activated by various exogenous agents such as bacteria and drugs. Clinical (feminine prevalence, frequent association with auto-immune diseases) and morphological similarities lead to argue and to hypothesis that both entities could represent different stages of the same disease, the lymphocytic colitis being the early stage. Various treatments have been proposed, for instance 5-aminosalicylates, but today mainly synthetic corticoids are used, especially budesonide. Others entities are recently been described: the chronic pericrypt eosinophilic enterocolitis and the colonic epithelial lymphocytosis ("epidemic").

Collagenous and lymphocytic colitis: systematic review and update of the literature.

Collagenous and lymphocytic colitis are well-described conditions causing chronic watery diarrhoea. A peak incidence from 60 to 70 years of age with a female predominance mainly in collagenous colitis is observed. Both conditions are characterised by a (near) normal colonoscopy, but with specific histologic findings on colonic biopsies. Histopathologically, both conditions are characterised by distinct epithelial abnormalities and a dense lymphoplasmocytic infiltrate. Distinct features consist of a characteristic collagen band deposition in the subepithelial layer in collagenous colitis and a markedly increased number of intra-epithelial lymphocytes in lymphocytic colitis. Although most cases are idiopathic, certain drugs can induce microscopic colitis. In addition, either condition can be associated with coeliac disease. For a long time patients with microscopic colitis were treated with non-specific anti-diarrhoeal agents, anti-inflammatory agents such as mesalazine, or systemic steroids, but with disappointing results. Bismuth subsalicylate was reported to be effective in a small controlled series of patients with collagenous colitis. Now, randomised controlled trials have shown the effectiveness of budesonide over placebo in collagenous colitis and more recently in lymphocytic colitis. The histologic response is variable, but a decrease in the subepithelial collagen layer and a decrease in the lymphoplasmocytic infiltrate in the lamina propria is observed in about half of the patients. In general, patients respond within 2 weeks with no major side effects. However, relapse is common (63-80% of patients) when budesonide is stopped. Longer-term treatment is effective but does not seem to reduce relapse rates upon discontinuation.

[Microscopic colitis: histopathological review with a clinicopathological correlation].

Microscopic colitis is a clinicopathological entity which, in addition to typical symptoms such as watery diarrhea, is characterized by its specific histopathology. Since colonoscopy yields normal findings, microscopic colitis belongs in a histological domain. The term encompasses two forms: lymphocytic and collagenous colitis. Histologically, lymphocytic colitis shows an increase in intraepithelial lymphocytes of more than 20 lymphocytes per 100 surface colonocytes, while collagenous colitis is characterized by a thickened subepithelial collagen layer of more than 10 µm. Specific stains help in the quantification of both. Since microscopic colitis does not always affect the entire colon and the number of intraepithelial lymphocytes varies physiologically, obtaining stepwise biopsies of the colon (with information on location where possible) is recommended. A thickened collagen layer is relatively specific for collagenous colitis, whereas intraepithelial lymphocytosis is also found in other diseases. Therefore, to make a correct diagnosis, it is important to correlate histological findings with clinical symptoms, including the main symptom of watery diarrhea.

[Collagen colitis and lymphocytic (microscopic) colitis: different or common origin?].

Collagenous and lymphocytic colitis are two chronic inflammatory colonic diseases characterized by chronic watery diarrhea. They can only be diagnosed by histological examination of colonic biopsies. The pathogenesis is unknown, but may be of an inflammatory possibly autoimmune nature. Others hypothesize that a bacterial toxin or another noxious luminal factor is responsible for the development of the microscopic colitis syndrome. Some studies suggest that NSAIDs may be an etiologic factor in collagenous colitis in a subgroup of patients with this disease. These disorders may be different entities, although some data support the possibility that they are only different manifestations of the same disease. Therapy with 5-aminosalicylate and in severe cases corticosteroids, is successful in most patients. The course of these chronic diseases is commonly benign and is characterized by periods of spontaneous remissions and relapses, but clinical and histopathological resolutions are occasionally seen. On the basis of our own two cases and the literature, these two diseases will be discussed. These patients were admitted to our hospital within a month of each other due to therapy-refractive chronic watery diarrhea. A 70-year-old woman had been suffering from diarrhea for more than ten years. The histological examination produced a diagnosis of collagenous colitis. Lymphocytic colitis was diagnosed from a histological examination in a 30-year-old man who had been suffering from diarrhea for six months. Both received a therapy of mesalazine and the symptoms disappeared within three weeks.

Chronic low-dose aspirin use does not alter colonic mucosa in asymptomatic individuals: a prospective cross-sectional study (STROBE 1a).

Aspirin may be involved in microscopic colitis (MC) development, but there are no data on colon histology in asymptomatic aspirin users. We prospectively assessed colonic and rectal mucosa from aspirin users, searching for MC features. From colonoscopy screenees, two biopsy samples were taken from each of three locations: ascending colon, transverse colon and rectum. A pathologist measured chronicity of inflammation and activity indicators, epithelial cell height and subepithelial collagen layer width. Intraepithelial lymphocytes (IELs), intralaminal eosinophils and apoptotic cells/100 crypts were counted. Panel data models were used to analyse associations between aspirin use, biopsy location and microscopic parameters. Of 100 screenees (age: 40-65 years), 42 were current aspirin users. Median duration of aspirin usage was 48 months (range: 36-60) with dosage ranging from 75-325 mg/day. We observed reduced epithelium polymorphs in subjects who used aspirin for <48 months versus non-users (p=0.008). Paneth cell metaplasia was significantly less frequent in aspirin users versus non-users (p=0.006). Inflammatory cells in lamina propria (eosinophils) and epithelium (IELs) were most abundant in the ascending colon and decreased distally (ascending colon vs transverse colon and transverse colon vs rectum). Cryptitis was more frequent in the ascending colon vs the rectum. We observed no specific MC features in asymptomatic chronic low-dose aspirin users. We found subtle physiological and histopathological differences between the bowel segments.

Collagenous colitis

Collagenous colitis is an inflammatory bowel disease affecting the colon specifically with peak incidence in the 5th decade of life, affecting women more than men. Its clinical presentation involves watery diarrhea in the absence of rectal bleeding. It is often classified under the umbrella entity microscopic colitis, that it shares with a related condition, lymphocytic colitis. Signs and symptoms Microscopic colitis causes chronic watery diarrhea with greater than 10 bowel movements per day. Some patients report nocturnal diarrhea, abdominal pain, urgency, fecal incontinence, fatigue, dehydration and weight loss. Patients report a significantly diminished quality of life. Causes The cause of collagenous colitis is unknown.

[Evolution of ideas on microscopic colitis].

The literature review gives the present-day views of the definition, etiology, pathogenesis, diagnosis, and treatment of microscopic colitis (MC). In the present view, MC is an inflammatory bowel disease of unknown etiology, which is characterized by chronic watery diarrhea, no macroscopic signs of large bowel involvement in the presence of specific pathomorphological changes. There are two major forms of MC, which are similar in its clinical picture, yet, heterogeneous in histological criteria: collagenous colitis (CC) and lymphocytic colitis (LC). As of now, the prevalence of MC is about 100 cases per 100,000 population, which is similar with that in other inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease. MC generally prevails in women aged over 50 years. The etiology and pathogenesis of MC have not fully investigated. Watery diarrhea is as a predominant pathognomonic symptom in all the patients with MC. The major histological criterion for the diagnosis of CC is subepithelial collagen lining thickening (more than 10 pm) and that for LC is higher intraepithelial lymphocyte counts (more than 20 intraepithelial lymphocytes/100 epitheliocytes). The topical glucocorticosteroid budesonide is currently the only agent, the efficacy of which has been proven in both inducing and maintaining remission in patients with MC in many clinical trials.

[Microscopic colitis - review].

Microscopic colitis (MC) is an encompassing term for two diseases; collagenous colitis and lymphocytic colitis. The colon appears normal by colonoscopy and a diagnosis is only obtained with a biopsy. The histopathology of collagenous colitis is mainly characterized by a thickening of the subepithelial basement membrane of the colonic mucosa with a band of collagen. Lymphocytic colitis is mainly characterized by an intraepithelial lymphocytosis without the collagen thickening. Even though the two diseases have a distinctive pathology their clinical symptoms are characterized by chronic watery diarrhea without bleeding. Microscopic colitis is thought to cause about 4-13% of all chronic diarrhea but their relative frequency is much higher among older people. The mean annual incidence for collagenous and lymphocytic colitis has been increasing. Steroids are the most effective treatment for microscopic colitis and budesonide is the most studied and effective therapy for MC. The aim of this paper is to give a review of two relatively new diseases which are among the most common cause of chronic diarrhea, especially among older people.


This is a patient with decompensated myasthenia with bulbar symptoms (dysphagia) and therefore risk of respiratory muscle involvement. The respiratory symptoms correspond to an exhaustion of the muscles, first inspiratory and then accessory (the patient does not appear fatigued or tachypneic because the muscles are exhausted), progressing to a carbonic coma.

A 64-year-old man, diagnosed with myasthenia gravis 1 year ago, treated with low-dose steroids (3 mg/day of deflazacort) and anticholinesterase drugs, asymptomatic for 6 months, consults for mild difficulty in swallowing and evening diplopia for a few days. He was admitted to the hospital for suspected myasthenic crisis and treatment was started. The next day the patient alerts at 03 hours in the morning because the patient makes a strange noise when breathing in, like a soft snoring, the patient is sound asleep and very sweaty, but does not seem to be fatigued. What is the most correct attitude?

Reassure the nurse and family that the patient is a habitual snorer and is peacefully asleep. The patient should be placed in lateral decubitus.

Notify intensive care for suspected acute respiratory failure, to assess possible orotracheal intubation and assisted ventilation.

Perform polysomnographic study to rule out sleep apnea.

Decrease steroid dose; if he has a steroid myopathy he will improve.

Order a thoracic CT scan to rule out compressive thymoma over the trachea associated with myasthenia.

A Case of COVID-19 With Myasthenic Crisis.

Coronavirus disease 2019 (COVID-19) infection can increase the risk of myasthenic crisis. Dexamethasone has been widely used to manage severe COVID-19 infection. Paradoxically, steroids are effective for treating myasthenia gravis; however, when they are started in high doses, there is an associated risk of steroid-induced exacerbation. This case report describes an 86-year-old male with seropositive generalised myasthenia gravis, whose course had been stable for years. At the time of his COVID-19 diagnosis, he was on pyridostigmine and prednisolone 10 mg daily. He was treated with IV dexamethasone 6 mg daily, remdesivir, and antibiotics. On day 10 of admission, he had a sudden deterioration with a Glasgow Coma Scale (GCS) score of 3. Arterial blood gas (ABG) showed a new type 2 respiratory failure suggesting myasthenic crisis. Although his ABG improved after commencing bilevel positive airway pressure (BiPAP), his condition continued to deteriorate and he died the next day. A decision not to intubate and ventilate had been made given his poor clinical state and low chance of recovery. His myasthenic crisis was likely precipitated by the COVID-19 infection, although steroids, azithromycin, and doxycycline also have the potential to cause the worsening of myasthenia gravis. Further studies are needed to evaluate the efficacy and risk of steroid use in this patient population. Ventilatory failure may occur insidiously and is often difficult to detect, especially in elderly and delirious patients in whom performing a neurological examination can be difficult. Regular ABG and bedside measures of forced vital capacity may be considered to monitor the development of type 2 respiratory failure.

Thymectomy during Myasthenic Crisis under Artificial Respiration.

A 34-year-old man was diagnosed with thymoma, which was evaluated preoperatively as stage II or III, with myasthenia gravis (MG). The size of the tumor was 70 × 44 × 80 mm. No invasion to neighboring organs was observed. Prednisolone was prescribed for stabilization of MG. However, a myasthenic crisis (MC) occurred, and intensive care, including emergent endobronchial intubation followed by artificial ventilation, pulse steroid therapy, high-dose intravenous immunoglobulin, and tacrolimus hydrate, was initiated. A chest computed tomography on day 6 revealed tumor reduction to 50 × 30 × 60 mm. An extended total thymectomy by median sternotomy was performed, and artificial ventilation was continued after that. Scheduled artificial ventilation and steroid therapy together can, therefore, enable complete resection of thymoma in patients undergoing treatment for MC. While ventilation helps avert a respiratory failure, the steroid therapy temporarily reduces the tumor size, making resection easier.

SOP myasthenic crisis.

The overall prevalence of myasthenic crisis is quite low at 30/1 million inhabitants because myasthenia gravis is a rare disease per se. But it should be noted that 15-20% of patients with myasthenia gravis experience at least one crisis in their lives. Most often, the crisis occurs within the first 2 years of the disease or is even the first manifestation of a yet undiagnosed myasthenia gravis in up to 20%.Median duration of MC is about 2 weeks (median 12-14 days of ventilation) under sufficient treatment, but prolonged courses are not uncommon and often due to comorbidities and complications, so that about 20% are still mechanically ventilated after 1 month.The lifetime risk of recurrence of a crisis is approx. 30%. Data on mortality differ between about 2-5% to even more than 16%. Lethal outcomes are almost never caused by the crisis itself, but because comorbidities or complications eventually become limiting. Myasthenic crisis (MC) is the life-threatening maximal manifestation of myasthenia gravis (MG) necessitating mechanical ventilation, supportive feeding and (neuro-)intensive care. Weakness may develop within minutes to days and encompass flaccid tetraparesis with immobility, severe dyspnea, respiratory insufficiency and aspiration. Globus events may be life threatening due to rapidly exhausting coughing and swallowing. ● Check and secure vital functions. ● not applicable. The main symptom of (imminent) myasthenic crisis is the rapidly progressive weakness of the respiratory and bulbar muscles, which lead to a decompensation with aspiration and respiratory insufficiency. Clinical examination and clinical history should lead early to the diagnosis of MG with (impending) crisis. The detection of red flags and the dynamic deterioration of symptoms entail admission to the intensive care unit. Due to bulbar symptoms with aspiration and/or respiratory insufficency, early intubation to secure the airway is essential. Therapy includes symptomatic treatment with pyridostigmine or neostigmine and acute causal treatment by immunoadsorption/plasmapheresis or alternatively with immunoglobulins. If used early, intubation may still be prevented and clinical improvement can be achieved within a few days. At the same time, immunosuppression with corticosteroids and azathioprine should be initiated or optimized. For escalation rituximab is an option. The early diagnosis and consequent treatment of infections and other complications such as delirium influence the further course.

[Acute iatrogenic myopathy during treatment of status asthmaticus. Our experience and review of the literature].

A young man was admitted to the ICU for acute asthmatic respiratory failure. He was sedated with propofol, curarized with pancuronium and put on mechanical ventilation for 15 day because of the persistent asthmatics crisis. Drug therapy for asthma included high-dose corticosteroids. When sedation and paralysis were stopped, the patient, that was fully conscious, showed flaccid quadriplegia. A muscular biopsy showed elective loss of the myosin thick filaments. Electrophysiologic evaluation was compatible with both neurologic or muscular pathology. The evolution of the disease was good; a drop-out performed 5 months later showed a complete motor recovery. This case report confirms that in some patients, intensive treatment of status asthmaticus may cause myopathy. Only recently this myopathy has been correlated to an interaction between steroids and neuromuscular blockers. Many experimental and clinical observations suggest a negative interaction between steroids and non-depolarizing curare derivatives. In the case reported here, diagnosis was based on electrophysiologic examination and above all on muscular biopsy. The occurrence of an acute toxic myopathy should always be taken into account, considering the high number of patients admitted with respiratory failure requiring steroid treatment and curare administrative for mechanical ventilation. It therefore seems reasonable to reduce steroid therapy as soon as possible with a periodic suspension of curare administration. Curare usage should be critically evaluated. Some basic examination such as serum CPK monitoring should allow early detection of muscular damage.

InternalMed_Harrison

Myasthenic crisis is defined as an exacerbation of weakness sufficient to endanger life; it usually consists of respiratory failure caused by diaphragmatic and intercostal muscle weakness. Crisis rarely occurs in properly managed patients. Treatment should be carried out in intensive care units staffed with teams experienced in the management of MG, respiratory insufficiency, infectious disease, and fluid and electrolyte therapy. The possibility that deterioration could be due to excessive anticholinesterase medication (“cholinergic crisis”) is best excluded by temporarily stopping anticholinesterase drugs. The most common cause of crisis is intercurrent infection. This should be treated immediately, because the mechanical and immunologic defenses of the patient can be assumed to be compromised. The myasthenic patient with fever and early infection should be treated like other immunocompromised patients. Early and effective antibiotic therapy, respiratory assistance (preferably

[A senile case of acute necrotizing myopathy presenting prolonged severe muscle paralysis due to high dose glucocorticoid and muscle relaxant].

An 82-year old man was admitted with dyspnea, productive cough and wheezing. In addition to antibiotics (meropenem trihydrate 0.5 g/day), glucocorticoids (hydrocortisone 1.250 mg, methylpredonisolone 4.250 mg) were administered for the severe bronchospasms. Since his respiratory condition deteriorated, he underwent mechanical ventilation using a muscle relaxant (vecuronium bromide, total dose 776 mg) in combination with high dose glucocorticoid. As his pneumonia improved on the 10th hospital day, we started weaning him from the ventilator. However, we were unable to complete weaning from the ventilator because of prolonged quadriplegia and paralysis of the respiratory muscles. A few days later, myoglobinuria appeared. Electrophysiological examinations suggested the involvement of both neuromuscular junctions and muscles. Muscle biopsy showed rhabdomyolysis. Acute necrotizing myopathy was diagnosed due to high doses of glucocorticoid, muscle relaxant, or both. He required about 3 months to be weaned from the mechanical ventilation, and another 3 months to leave the hospital. Based on our experience, we should consider acute myopathy as an adverse effect of glucocorticoids, muscle relaxants or both in elderly patients who require mechanical ventilation.

Neurology_Adams

General medical care In severe cases, respiratory assistance and assiduous nursing are paramount, because the disease remits naturally and the outlook for recovery is favorable in the majority of patients. About one-quarter of our patients have required mechanical ventilation. Because a patient’s condition may deteriorate unpredictably and rapidly in the first days of illness, virtually all but the mildest cases should be admitted to the hospital for observation of respiratory, autonomic, and motor function. The comments that follow are applicable to most other forms of acute and subacute neuromuscular respiratory failure, including myasthenia gravis and high spinal cord injury.

Neurology_Adams

Patients with myasthenic crisis generally respond to plasma exchange or to immunoglobulin infusions in 1 or 2 days, but more often a week or more is required for recovery after a full course of 4 to 5 exchanges or 3 to 5 g/kg IVIg given in divided daily doses. Whether the previously mentioned studies (e.g., Gajdos et al) comparing the 2 treatments and comparing doses of IVIg in myasthenic exacerbations are pertinent to crisis is unknown but we almost always institute one or the other soon after it as it is apparent that respiratory failure is imminent or worsening.

Ocular myasthenia

Patients with mild-to-moderate ocular myasthenia are usually treated initially with oral anticholinesterase agents, Mestinon (pyridostigmine) being the most commonly employed. There have not been any randomized clinical trials conducted with these agents, and this treatment is often unsuccessful, particularly in resolving diplopia. Immunosuppressive therapy is then started and the agent of choice is usually prednisone. In a small controlled study this drug demonstrated greater efficacy than pyridostigmine. Steroid therapy is controversial, but in another study the results suggested that prednisone does decrease progression to generalized MG. There is no single recommended dosing regimen in light of the side effects commonly associated with chronic corticosteroid therapy, and the difficulty in weaning patients from steroids without exacerbation of symptoms. Response to prednisone therapy is variable.

Neurology_Adams

It is generally best to wait 2 or 3 weeks before committing a patient to tracheostomy. When weaning from the ventilator is anticipated, anticholinesterase agents are reintroduced slowly, and treatment with corticosteroids can be instituted if necessary. Oral doses of 60 mg pyridostigmine or 15 mg neostigmine are roughly equivalent to 0.5 to 1 mg neostigmine intravenously and 1.5 to 2 mg intramuscularly, as noted in Table 46-1. The management of the critically ill patient with myasthenia is reviewed in the monograph by Ropper and colleagues.

InternalMed_Harrison

Glucocorticoid Therapy Glucocorticoids, when used properly, produce improvement in myasthenic weakness in the great majority of patients. To minimize adverse side effects, prednisone should be given in a single dose rather than in divided doses throughout the day. The initial dose should be relatively low (15–25 mg/d) to avoid the early weakening that occurs in up to one-third of patients treated initially with a high-dose regimen. The dose is increased stepwise, as tolerated by the patient (usually by 5 mg/d at 2to 3-day intervals), until there is marked clinical improvement or a dose of 50–60 mg/d is reached. This dose is maintained for 1–3 months and then is gradually modified to an alternate-day regimen over the course of an additional 1–3 months; the goal is to reduce the dose on the “off day” to zero or to a minimal level. Generally, patients begin to improve within a few weeks after reaching the maximum dose, and improvement continues to progress for months or years. The

[Myasthenia gravis presenting as isolated respiratory failure].

A 61-year-old woman in excellent health and taking no medications presented with progressive dyspnea on exertion. She did not exhibit diplopia, dysphagia, dysarthria or muscle weakness. Her condition deteriorated, and respiratory distress developed. The patient was intubated and placed on mechanical ventilation. A computed tomogram of her chest revealed a moderately enlarged thymus gland unsuspected on a plain x-ray film. Myasthenia gravis was diagnosed on the basis of a high acetylcholine receptor antibody titer. Treatment started with prednisolone, anticholinesterase agent, and plasma exchange. The patient underwent a thymectomy 3 weeks after her diagnosis. Her symptoms were brought under control by anticholinesterase agent and prednisolone. This case illustrates the need to consider myasthenia gravis as well as other motor-neuron disorders when evaluating individuals presenting acute respiratory failure of unknown origin.

Clinical Management of Pneumonitis in Patients Receiving Anti-PD-1/PD-L1 Therapy.

<bCASE STUDY</b A 48-year-old gentleman with metastatic melanoma currently receiving the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, ipilimumab (Yervoy), and the programmed cell death protein 1 (PD-1) inhibitor, nivolumab (Opdivo), returned for evaluation prior to receiving cycle 2. The patient presented with new onset dyspnea and a non-productive cough over the past week, with a temperature of 100.6°F at home on one occasion. He was placed on observation for fever, cough, and shortness of breath. The patient had no previous history of lung disease and was a nonsmoker. Diminished breath sounds were noted on auscultation. However, the patient was without fever or chills, with a heart rate of 101 beats per minute and a blood pressure of 110/75 mm Hg. We obtained a computed tomography (CT) of his chest. The CT demonstrated diffuse ground-glass opacities in his bilateral lower lobes and some minor interstitial thickening of his right middle lobe, possibly suggestive of inflammation or cryptogenic organizing pneumonia. Based on his presentation and CT findings, the patient was initially treated empirically with antibiotics for suspected pneumonia vs. pneumonitis. During the first 12 hours in observation, the patient experienced increasing dyspnea and cough and was admitted to the hospital. Nebulizer treatments were administered with no improvement, so the patient was started on high-dose corticosteroids at 1 mg/kg, and pulmonary and infectious disease consults were ordered. After the administration of steroids, the patient's cough and breathing improved and he remained afebrile, eliciting a high suspicion for immune-related pneumonitis. The patient then underwent bronchoscopy to rule out other etiologies. Bronchoalveolar lavage was performed, which yielded no pathogenic organisms. The patient was placed on a 3-week course of a high-dose steroid taper, following which immunotherapy was reinstated. Within 4 days he again presented with similar symptoms, was restarted on high-dose steroids, and immunotherapy was permanently discontinued.

[Intensive care in myasthenic and cholinergic crises].

Presents the epidemiology, possible etiology, and pathogenesis of myasthenia, methods of diagnosis of the disease, and clinical picture of critical states. Describes the present-day methods of treating myasthenic and cholinergic crises: programmed plasmapheresis combined with hormone therapy, pulsed therapy with superhigh doses of corticosteroids, and the most novel method for the treatment of autoimmune diseases, intravenous infusions of immunoglobulins. Draws attention to indications for artificial ventilation of the lungs and tracheostomy. Enumerates the drugs which are not recommended for patients with myasthenia. Emphasizes that the use of the whole complex of modern therapeutic methods for the treatment of grave myasthenia helps reduce the mortality to virtually null.

Allergic bronchopulmonary aspergillosis

In order to mitigate these risks, corticosteroid doses are decreased biweekly assuming no further progression of disease after each reduction. When no exacerbations from the disease are seen within three months after discontinuing corticosteroids, the patient is considered to be in complete remission. The exception to this rule is patients who are diagnosed with advanced ABPA; in this case, removing corticosteroids almost always results in exacerbation and these patients are continued on low-dose corticosteroids (preferably on an alternate-day schedule). Serum IgE can be used to guide treatment, and levels are checked every 6–8 weeks after steroid treatment commences, followed by every 8 weeks for one year. This allows for a determination of baseline IgE levels, though it's important to note that most patients do not entirely reduce IgE levels to baseline. Chest X-ray or CT scans are performed after 1–2 months of treatment to ensure infiltrates are resolving.

Myasthenia gravis complicated with primary aldosteronism and hypokalemic myopathy.

A 34-year-old Japanese man was admitted to an outside hospital with an elevated creatinine kinase level and suspected myositis. He was treated with high dose methylprednisolone, which caused severe aggravation of muscle weakness. He was transferred to our hospital at that time. On admission, chest computed tomography (CT) and the presence of anti-acetylcholine receptor antibodies supported a diagnosis of myasthenia gravis and thymoma. Laboratory findings showed hypokalemia, low plasma renin activity and high serum aldosterone. Further studies, including abdominal CT and adrenal venous sampling suggested primary aldosteronism. At first, thymectomy was performed, and one month later, he was treated with laparoscopic adrenalectomy. Immediately after this procedure, he suffered from myasthenic crisis, which was successfully managed with mechanical ventilation and steroid pulse therapy followed by oral prednisolone. This case presented a serious difficulty in differentiating from various myopathies and giving proper treatment because of a rare combination of independent diseases and their masquerading clinical features.

InternalMed_Harrison

on the “off day” to zero or to a minimal level. Generally, patients begin to improve within a few weeks after reaching the maximum dose, and improvement continues to progress for months or years. The prednisone dosage may gradually be reduced, but usually months or years may be needed to determine the minimum effective dose, and close monitoring is required. Few patients are able to do without immunosuppressive agents entirely. Patients on longterm glucocorticoid therapy must be followed carefully to prevent or treat adverse side effects. The most common errors in glucocorticoid treatment of myasthenic patients include (1) insufficient persistence—improvement may be delayed and gradual; (2) tapering the dosage too early, too rapidly, or excessively; and (3) lack of attention to prevention and treatment of side effects.

Myasthenia in a patient with sarcoidosis and schizophrenia.

A 44-year-old male patient was hospitalised with paranoid schizophrenia in 1985. Depot neuroleptic treatment was started which successfully prevented further psychotic relapses for the next ten years. His myasthenia gravis started with bulbar signs in 1997 and the symptoms soon became generalized. The diagnosis of myasthenia gravis was confirmed by electromyography, by positive anticholinesterase test and by the detection of anti-acetylcholine receptor antibodies in the serum. Mediastinal CT examination showed enlarged hilar lymph nodes on the left but no thymic pathology was observed. Mediastinoscopy was performed and biopsies were obtained from the affected nodes. Histology revealed sarcoidosis. The patient suffered respiratory crisis following the thoracic intervention (in September 1998). Combined oral corticosteroid (64 mg methylprednisolone/e.o.d.) and azathioprine (150 mg/day) treatment regimen was initiated and complete remission took place in both the myasthenic symptoms and the sarcoidosis. The follow-up CT scans showed no mediastinal pathology (January 2000). During steroid treatment a transient psychotic relapse occurred which was successfully managed by supplemental haloperidol medication added to his regular depot neuroleptics. The patient currently takes 150 mg/day azathioprine and receives 40 mg/month flupentixol depot i.m. His physical and mental status are stable and he has been completely symptom free in the last 24 months. The association of myasthenia gravis and sarcoidosis is very rare. To our best knowledge no case has been reported of a patient suffering from myasthenia gravis, sarcoidosis, and schizophrenia at the same time.

Myasthenia gravis in conjunction with Graves' disease: a diagnostic challenge.

To describe an association between Graves' disease and myasthenia gravis and discuss the clinical features and laboratory tests that may help distinguish these two diseases. The clinical, laboratory, and electrophysiologic findings in a patient with Graves' disease and myasthenia gravis are presented. A 28-year-old African American man was admitted to the University of Louisville Hospital with generalized muscle weakness, exophthalmos, diplopia, weight loss, and mild dysphagia. The diagnosis of Graves' disease with ophthalmologic involvement was suspected clinically and confirmed by an undetectable thyrotropin level (<0.03 mIU/mL), high total thyroxine (20.5 mg/dL), and increased homogeneous 123I thyroid uptake. Because of the generalized muscle weakness and mild dysphagia, assessment was done by a neurology team, and severe thyrotoxic myopathy was diagnosed. He was treated with 131I and b-adrenergic blocking agents and scheduled for follow-up as an outpatient. Two weeks later, the patient presented in acute respiratory failure. The neurology team was reconsulted because of suspected myasthenic crisis. Anti-acetylcholine receptor antibodies were undetectable in the serum, and computed tomography of the chest showed no thymic enlargement. Repetitive nerve stimulation testing, however, showed findings consistent with an abnormality of the neuromuscular junction. The patient responded dramatically to an anticholinesterase agent and corticosteroids. The overlapping clinical features may cause diagnostic confusion when myasthenia gravis and Graves' disease coexist, and numerous tests may be needed to distinguish these two conditions, which have differing treatments and prognoses.

An Unusual Case of Dilated Cardiomyopathy in Wegner's Granulomatosis.

A 33-year-old male presented to the emergency with cough, hemoptysis, and shortness of breath. He was on steroids for suspected Still's disease due to arthralgias and fever prior to presentation to the emergency. He developed sudden hypoxic respiratory failure and required mechanical ventilation. The initial imaging studies of the chest including computed tomography (CT) of the chest showed marked diffuse central and basilar predominant opacities with associated smooth septal thickening. Furthermore, the patient's creatinine, troponin, B-type natriuretic peptide (BNP), rheumatoid factor, and D-dimer were elevated. Vasculitis workup, bronchoscopy, and echocardiogram were performed. The echocardiogram revealed severely decreased left ventricular systolic function with an ejection fraction of 24% with dilated left ventricle. The electrocardiogram did not show any findings of acute ischemia. He was started on pulse dose steroid and dobutamine drip along with intermittent diuresis. The patient was successfully extubated after two days of mechanical ventilation. He was started on cyclophosphamide in the hospital. Dobutamine was discontinued. He was moved to the general medical floor as his oxygenation improved, but later at night, he developed respiratory failure and required a bumetanide drip. The cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA) (anti-PR-3 antibody) came back positive with titer >1:40, so Wegner's granulomatosis was diagnosed. He received three sessions of plasmapheresis. The patient's kidney function improved significantly, and the bumetanide drip was transitioned to intravenous pushes. His oxygenation improved significantly with saturations of 92% on room air. The patient was discharged on steroid, Bactrim, and systolic heart failure medications to follow up with rheumatology, nephrology, pulmonology, and cardiology in the office. Due to insurance issues, his outpatient care was delayed significantly. The patient followed up with rheumatology after two months and has been planned for rituximab induction and to continue steroid along with Bactrim. This case is worth reporting because it describes dilated cardiomyopathy (DCM) as a cardiac manifestation of Wegner's granulomatosis. Early cardiac evaluation should be incorporated into the management of the patient suspected of Wegner's granulomatosis.

Effective treatment of a 13-year-old boy with steroid-dependent ocular myasthenia gravis using tacrolimus.

Over the past several years, tacrolimus has attracted attention as a new therapeutic drug for myasthenia gravis (MG), but few reports have considered its use for MG in pediatric patients, and most of these have focused on severe systemic MG. In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis. He first showed symptoms of ocular MG at age 2 years 3 months. At age 13 years, he was receiving PSL (3.75 mg/day), but the symptoms of ocular MG recurred. We increased the dosage of oral PSL up to 30 mg/day, and three courses of mPSL pulse therapy were applied, but these therapies had only limited effect, and his symptoms worsened. Tacrolimus was started at 0.4 mg/day (0.011 mg/kg/day), and every 2 weeks the dose was gradually increased by 0.2 mg/day. His symptoms of MG began to improve 3 weeks after the initial administration of tacrolimus. Approximately 3 months after the start of tacrolimus administration, PSL was discontinued. Currently, at 1 year and 4 months after the start of tacrolimus administration, while slight ptosis is observed in the evening, it does not influence his daily life, and his condition remains comparable to that when he stopped taking PSL. No adverse effects of tacrolimus have been recognized. In pediatric patients with steroid-dependent ocular MG without thymectomy, tacrolimus may be a safe and effective alternative to steroid and thymectomy.

Neurology_Adams

A rapid and severe deterioration of the myasthenia, termed myasthenic crisis, can bring the patient to the brink of respiratory failure in a matter of hours. A respiratory infection or excessive use of sedative medications or drugs with a potential for blocking neuromuscular transmission may precede the myasthenic crisis. We have encountered numerous cases in which oropharyngeal weakness has led to aspiration pneumonia, which, in turn, precipitated a crisis. Just as often, a precipitating event is not evident. Rarely, a respiratory arrest is the first manifestation of crisis. Such events may occur at any time after the diagnosis of myasthenia, but half are evident within 12 to 18 months. In an early but still salient experience with 53 patients in myasthenic crisis at the Columbia-Presbyterian Medical Center, pneumonia was the most frequent precipitating event, but no cause could be determined in almost one-third of cases (Thomas et al).

Polysomnography

Pulse oximetry determines changes in blood oxygen levels that often occur with sleep apnea and other respiratory problems. The pulse oximeter fits over a fingertip or an earlobe. Snoring may be recorded with a sound probe over the neck, though more commonly the sleep technician will just note snoring as "mild", "moderate" or "loud" or give a numerical estimate on a scale of 1 to 10. Also, snoring indicates airflow and can be used during hypopneas to determine whether the hypopnea may be an obstructive apnea. Procedure For the standard test, the patient comes to a sleep lab in the early evening and over the next 1–2 hours is introduced to the setting and "wired up" so that multiple channels of data can be recorded when he/she falls asleep. The sleep lab may be in a hospital, a free-standing medical office, or in a hotel. A sleep technician should always be in attendance and is responsible for attaching the electrodes to the patient and monitoring the patient during the study.

[Myasthenic Crisis].

Myasthenic crisis is the life threatening maximal manifestation of myasthenia gravis. Severe dysphagia and respiratory insufficiency demand admission to an intensive care unit (ICU). At variance, the timely recognition and treatment of myasthenic exacerbation may prevent a manifesting crisis. This reviews deals with red flags that pronounce exacerbation and crisis. Myasthenic crisis is an important differential diagnosis of bulbar symptoms and dysphagia. We elaborate on a structured and comprehensive approach to myasthenic crisis on the ICU. Hallmarks of therapy are symptomatic treatment with acetylcholine esterase inhibitors, plasmapheresis or immunoadsorption, polyvalent immunoglobulins, an early start of steroids and immunosuppressants, namely azathioprine, and a consequent escalation to monoclonal antibody therapy, with rituximab being the first choice. Special demands in ICU treatments are a structured weaning concept, consequent treatment of comorbidities and complications, first and foremost infections, dysphagia management, and comprehensive prevention and treatments of delirium.

The Pulmonary Complications of Paraneoplastic Autoimmune Vasculitis in a Patient With Myelodysplastic Syndrome.

Paraneoplastic autoimmune phenomena may occur in up to 30% of patients with myelodysplastic syndrome (MDS). We present the case of a patient with MDS who developed diffuse alveolar hemorrhage due to paraneoplastic autoimmune vasculitis. The patient was a 55-year-old male who had been referred for outpatient hematology/oncology evaluation by his primary care physician for incidentally discovered thrombocytopenia. When he presented to the clinic, he reported new-onset chills, weakness, and night sweats. He endorsed a 20-pound weight loss over two months as well as two weeks of fatigue, exertional dyspnea, and epistaxis. He was noted to be ill-appearing and had bilateral pitting edema to the knees. Vital signs revealed a temperature of 102.3 °F, oxygen saturation of 84% on room air, and tachycardia to the 90s. Labs showed hemoglobin of 5.7 g/dL, hematocrit of 17.2 g/dL, and platelet count of 27 kµL. He was admitted to the hospital for blood and platelet transfusions, empiric antibiotics, and further diagnostic studies. The peripheral blood smear showed 4% blasts and frequent dyspoietic granulocytes. Bone marrow biopsy (BMB) was performed to differentiate between acute leukemia and myelodysplasia. BMB revealed myelodysplasia with excess blasts and erythroid predominance.During hospitalization, the patient developed acute hypoxemic respiratory failure due to bronchoscopy-confirmed diffuse alveolar hemorrhage from thrombocytopenia. His platelet count was 12 kµL. High-dose corticosteroids (2 mg/kg prednisone) were initiated for suspected paraneoplastic autoimmune vasculitis, pending BMB results. The patient steadily improved, was extubated, and had reduced oxygen and transfusion requirements.High-dose steroids were stopped, and the patient was started on decitabine chemotherapy with the ultimate goal of bone marrow transplantation. On day five of decitabine, the patient developed acute hypoxic respiratory failure requiring intubation as well as hypotension requiring vasopressors. Given that recurrent diffuse alveolar hemorrhage was again suspected, high-dose steroids were resumed upon transfer to the ICU. He continued to decompensate and ultimately experienced ventricular tachycardia requiring three separate episodes of cardiopulmonary resuscitation. Per the family's wishes, he was palliatively extubated, and he expired an hour later. Diffuse alveolar hemorrhage is a rare but potentially deadly pulmonary complication of MDS, stemming from a paraneoplastic autoimmune vasculitis. Patients who initially present with atypical autoimmune phenomena should raise suspicion for an underlying MDS, the presence of which can guide the promptness, extent, and duration of immunosuppressive therapy. Failure to expeditiously treat these patients with corticosteroids can lead to serious complications and death.

[Emergencies in neuromuscular pathology].

Acute muscle weakness (AMW) is the predominant symptom of neuromuscular emergencies, especially if it affects the respiratory or oropharyngeal musculature . AMW is a multi-etiological syndrome, with different lesion levels in the motor unit. Within the broad group of neuromuscular diseases, those that most frequently provoke AMW and respiratory failure are Guillain-Barré syndrome (GBS) and myasthenia gravis (MG). GBS is the most frequent cause of acute flaccid paralysis; it can cause respiratory failure in a third of cases, making mechanical ventilation necessary. Accurate diagnosis of this syndrome enables immunomodulatory treatment to be started, which has been shown to modify the course of the disease. Besides, clinical evaluation of the patients and knowledge of the simple tests of neurophysiology and respiratory function will guide the decision on mechanical ventilation, avoiding emergency intubation. The most frequent emergency caused by MG is myasthenic crisis, defined by the deterioration in the bulbar function with acute respiratory insufficiency and risk of respiratory stoppage. This occurs in 15-20% of myasthenic patients and can be triggered by numerous factors. Besides early identification of the crisis, it is important to suppress the triggering factors and to provide measure of ventilatory support. Amongst the pharmacological measures, the most useful instruments at present are plasmapheresis and intravenous immunoglobulins; these treatments do not cancel the need for intensive vigilance and of checking for imminent signs of respiratory failure that will involve invasive or non-invasive ventilatory support.

InternalMed_Harrison

Anticholinesterase medication produces at least partial improvement in most myasthenic patients, although improvement is complete in only a few. Patients with anti-MuSK MG generally obtain less benefit from anticholinesterase agents than those with AChR antibodies. Pyridostigmine is the most widely used anticholinesterase drug. The beneficial action of oral pyridostigmine begins within 15–30 min and lasts for 3–4 h, but individual responses vary. Treatment is begun with a moderate dose, e.g., 30–60 mg three to four times daily. The frequency and amount of the dose should be tailored to the patient’s individual requirements throughout the day. For example, patients with weakness in chewing and swallowing may benefit by taking the medication before meals so that peak strength coincides with mealtimes. Long-acting pyridostigmine may occasionally be useful to get the patient through the night but should not be used for daytime medication because of variable absorption. The maximum useful

Pre-Descemet's Endothelial Keratoplasty

Postoperative Care Post operatively these patients are given topical steroids and antibiotics for 1 month. Low dose steroids are kept in maintenance for one year. Topical lubricants are prescribed according to the ocular surface changes. Preservative free lubricants are initiated in patients with immediate epithelial changes. Intraocular pressure is monitoring on regular basis to assess the steroid induce glaucoma. Follow up visits are preferred as day 1, day 3, day 7, 2 weeks, 1 month, 3 months and then 6 monthly. Post operative anterior segment optical coherence tomography may be performed for assessing the anatomical success of the technique. Advantages

Case Report of Multisystem Inflammatory Syndrome in Adults (MIS-A): A 31-Year-Old Man with Fever, Rash, and Cardiac Symptoms 6 Weeks Following SARS-CoV-2 Infection, Successfully Resuscitated Following Cardiac Arrest.

BACKGROUND Multisystem inflammatory syndrome in adults (MIS-A) is an uncommon condition after a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, manifesting as multiorgan failure despite apparent resolution of initial symptoms. While this syndrome shares similar characteristics with a syndrome found in children, fewer cases are reported in adults. This report details a 31-year-old man fulfilling the diagnostic criteria of MIS-A, who was successfully resuscitated following cardiac arrest. CASE REPORT A 31-year-old man was admitted to the intensive care unit for 3 days of progressively worsening fever, chills, diaphoresis, exanthematous rash, headache, and neck stiffness. The patient had a history of mild, resolved SARS-CoV-2 infection 6 weeks prior to his presentation, diagnosed by rapid antigen and reverse transcription polymerase chain reaction (RT-PCR) testing. Meningitis and autoimmune pathologies were initially suspected but were ruled out. Given the patient's symptoms, prior SARS-CoV-2 infection, and positive inflammatory markers, findings correlated with the Centers for Disease Control and Prevention's diagnostic criteria for multisystem inflammatory syndrome in adults. On hospital day 1, the patient decompensated into severe respiratory distress requiring intubation. Shortly after, the patient developed cardiac arrest and was successfully resuscitated. He was transferred from our rural hospital to an intensive care unit at a facility with additional resources. He remained critically ill for several weeks while receiving high-dose steroids, intravenous immunoglobulin (IVIG), and hemodialysis until his recovery. CONCLUSIONS Early diagnosis and treatment of MIS-A would significantly improve outcomes in this subset of patients, especially in clinical settings with limited resources.

Neurology_Adams

In Simpson’s opinion, and this coincides with our observations, the danger of death from generalized myasthenia gravis is greatest in the first year after onset of the disease. A second period of danger in progressive cases is from 4 to 7 years after onset. After this time, the disease tends to stabilize and the risk of severe relapse diminishes. Fatalities relate mainly to the respiratory complications of pneumonia and aspiration. The mortality rate in the first years of illness, formerly in excess of 30 percent, is now less than 5 percent and with appropriate therapy virtually all patients lead normal lives.

Myasthenic crisis and late deep vein thrombosis following thymectomy in a patient with myasthenia gravis: A case report.

Surgical stress and pain are potential provoking factors for postoperative myasthenic crisis (POMC). We report the occurrence of early POMC and late deep vein thrombosis (DVT) in a man with myasthenia gravis (MG) undergoing thymectomy, addressing possible link between reversal of opioid overdose with naloxone and the triggering of POMC. A 71-year-old man with impaired renal function (ie, estimated glomerular filtration rate [egfr]: 49.1 mL/min/1.73 m) with diagnosis of MG made 2 months ago was scheduled for thymectomy. After uncomplicated surgery, he experienced opioid overdose that was treated with naloxone. Hyperlactatemia then developed with a concomitant episode of hypertension. Three hours after reversal, he suffered from myasthenic crisis presenting with respiratory failure and difficult weaning from mechanical ventilation. Stress-induced hyperlactatemia and subsequent myasthenic crisis INTERVENTIONS:: Pyridostigmine and immunosuppressive therapy with prednisolone were initiated. Hyperlactatemia subsided on postoperative day (POD) 5. Tracheal extubation was performed successfully on POD 6. During the course of hospitalization, his eGFR (ie, 88.9 mL/min/1.73 m) was found to improve postoperatively. After discharge from hospital, he developed DVT in the left femoral and popliteal veins on POD 24 when he was readmitted for immediate treatment with low-molecular-weight heparin. He was discharged without sequelae on POD 31. There was no recurrence of myasthenic crisis or DVT at 3-month follow-up. Following naloxone administration, hyperlactatemia may be an indicator of pain-related stress response, which is a potential provoking factor for myasthenic crisis. Additionally, patients with MG may have an increased risk of DVT possibly attributable to immune-mediated inflammation. These findings highlight the importance of perioperative avoidance of provoking factors including monitoring of stress-induced elevations in serum lactate concentration, close postoperative surveying for myasthenic crisis, and early recognition of possible thromboembolic complications in this patient population.

Myasthenic crisis.

Myasthenic crisis is a serious occurrence, affecting up to 27% of patients with myasthenia gravis. In the approach to the patient with myasthenic crisis, (1) the diagnosis of myasthenia gravis is confirmed; (2) respiratory failure is evaluated and treated in the intensive care unit, while potential precipitating factors are identified and managed; (3) immunomodulatory treatment is initiated; and (4) complications are avoided or managed promptly. The mortality rate should be 5% or less, with the elderly being most vulnerable.