Whipple's Disease, An Overlooked Diagnosis

Whipple disease is a rare multisystem inflammatory disease. Because fewer than 1000 reported cases have been described, clinical experience with this disorder is sparse. We are reporting a case of a 46-year-old man who presented with fever, weight loss, and polyarthralgia for 2 months, and 1 month of diarrhea. The patient was thoroughly investigated for collagen diseases and COVID-19, with no definite diagnosis. A therapeutic trial by immunosuppressive drugs provided partial remission followed by a marked rebound of the symptoms. His occult blood in stool was positive and subsequent upper endoscopy with proximal small intestinal biopsies showed the pathological features of Whipple's disease. The patient showed a dramatic improvement following treatment with ceftriaxone and trimethoprim-sulfamethoxazole. Despite the rarity of Whipple's disease, its course mimics many rheumatological diseases, inflammatory bowel disease, and COVID-19 disease. It should always be a part of the differential diagnosis of obscure polyarthralgia and chronic diarrhea.Copyright © 2023 The Author(s).

Viral enteritis in cattle: To well known viruses and beyond

Livestock products supply about 13 percent of energy and 28 percent of protein in diets consumed worldwide. Diarrhea is a leading cause of sickness and death of beef and dairy calves in their first month of life and also affecting adult cattle, resulting in large economic losses and a negative impact on animal welfare. Despite the usual multifactorial origin, viruses are generally involved, being among the most important causes of diarrhea. There are several viruses that have been confirmed as etiological agents (i.e., rotavirus and coronavirus), and some viruses that are not yet confirmed as etiological agents. This review summarizes the viruses that have been detected in the enteric tract of cattle and tries to deepen and gather knowledge about them.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Rapid disease progression after enzyme replacement therapy interruption in a patient with cholesteryl ester storage disorder

Lysosomal acid lipase deficiency (LALD) has two clinical phenotypes: an infantile-onset form - Wolman disease (WD) presented by severe malabsorption, cholestasis, malnutrition, hepatosplenomegaly and early death, and a later-onset form - cholesteryl ester storage disorder (CESD) with hepatosplenomegaly, dyslipidemia, malabsorption and variable disease severity manifestation. Enzyme replacement therapy (ERT) with sebelipase alfa was approved by the Brazilian Health Regulatory Agency (ANVISA) in 2017. We report the deleterious effect of ERT interruption in a CESD patient. Male, 16y, diagnosed at 7y, positive familiar history with mother, grandfather and three siblings affected. He was enrolled in the phase 3 clinical trial from age 9-12y under the 3 mg/Kg dose regimen. Then he enrolled in the post-study donation program under the same dose. Due to personal, importation and supply issues, and the COVID-19 pandemic restrictions, he had a progressive decrease in treatment adherence rate: 68% at 12y, 27% at 13y, 30% at 14y and after that he had an interruption of 1 entire year. At 15y he presented with generalized edema, severe fatigue, tachycardia, was hospitalized, diagnosed low serum iron, albumin and protein, acute anemia (hemoglobin: 6.2 g/dL - normal range of 12,5-13,5), and received blood transfusion. In the next year, still without ERT, he was hospitalized again due to generalized edema, acute anemia (Hemoglobin = 6.9 g/dL) and worsening of hypoalbuminemia and iron deficiency, and received blood transfusion. Although our patient has the CESD phenotype, the ERT interruptions did not worsen the liver involvement nor the dyslipidemia, but caused a severe malabsorption which is classically described in WD phenotype. In conclusion, this case serves as an alert that when ERT is interrupted, there is a rapid clinical deterioration. Acknowledgements: to IGEIM, and Drs Felippe Raphael e Oliveira Previdi and Ana Eduarda Saraiva Pereira Campos for clinical assistance of the patient.

The role of membrane and circulating forms of ACE 2 in pathological processes in COVID-19 infection

The review analyzes milestone information about the function and pathogenic significance of human angiotensin-converting enzyme 2 (ACE 2). ACE 2 is involved in the development of diseases such as hypertension, malabsorption of certain amino acids in the intestine, and a new type of pneumonia COVID-19 caused by the SARS-CoV-2 virus. Based on the latest literary sources, an assessment is made of the role of differential expression of receptor and soluble forms of this protein in the functioning of the renin-angiotensin-aldosterone system, as well as the mechanisms of ACE 2 participation in the sequential chemical conversion of angiotensin II and its effect on the function of the cardiovascular system. The role of ACE 2 in the development of inflammatory processes in the intestine and its effect on the composition of the intestinal microbiota are also discussed. In addition, the review presents most general data on the proteolytic activation of the S-glycoprotein of the SARS-CoV-2 virus and its participation, together with ACE 2, in the process of virus introduction into the host cell. In conclusion, the hypothesis about autoimmune complications of COVID-19 associated with the formation of the S-glycoprotein-ACE 2 immune complex and the production of autoantibodies is considered. Copyright © 2021 All-Russian Public Organization Antihypertensive League. All rights reserved.

Prompt Diagnosis and Intervention of Oxalate Nephropathy to Salvage Kidney Function

Hyperoxaluria can be primary due to defective glyoxylate metabolism leading to hepatic oxalate overproduction or secondary due to increased intestinal oxalate absorption. Oxalate nephropathy is the deposition of calcium oxalate crystals leading to tubular injury, interstitial fibrosis, and AKI or CKD. This describes three cases of renal oxalosis. First is a 60 year old male with stroke, hypertension, diabetes who presented with AKI of 4.5 mg/dL from 1.6 that rose to 11 mg/dL. Serologies for glomerulonephritis and paraproteinemia were negative. Biopsy showed tubular oxalate crystal deposition with tubular injury and interstitial nephritis. His renal failure required dialysis. Second is a 58 year old female with gastric bypass surgery who presented for edema and AKI from 1.3 to 3.6 mg/dL. Serologies were also negative. Biopsy showed interstitial nephritis with tubular calcium oxalate deposition. She was started on prednisone 60 mg. Creatinine stabilized to 2.2 mg/dL, not requiring dialysis. Third is a 82 year old male with obesity and sarcoma of the scalp treated with pembrolizumab who presented with dyspnea, edema and an AKI from 1 to 8.6 mg/dL. Urine sediment was bland with negative serologies. Differential included AIN due to pembrolizumab. Patient was started on high dose prednisone and biopsy showed interstitial nephritis and calcium oxalate crystal deposition. Patient endorsed taking frequent vitamin C as prophylaxis for Covid. Creatinine stabilized to 2.9 mg/dL not on dialysis. Classic etiologies of hyperoxaluria include dietary oxalate from ascorbic acid and fat malabsorption from gastric bypass surgery. Treatment includes increased fluid intake, oral calcium supplements and low oxalate diet. Oxalate nephropathy remains an under recognized cause of kidney failure, as such, early biopsy and intervention are necessary. (Figure Presented)

VITAMIN C NEPHROTOXICITY IN A COVID-19 PATIENT: A CASE REPORT

BACKGROUND AND AIMS: During the time of the COVID-19 pandemic, multiple treatment options have been investigated, even though their efficacy and secondary effects remain insufficiently known. We report the case of a vitamin C induced oxalate nephropathy in a COVID-19 patient with preexisting chronic kidney disease (CKD) resulting in irreversible acute renal failure. Vitamin C, also known as ascorbic acid, has been used as an anti-inflammatory therapy for COVID-19, but review of the literature shows similar cases of acute kidney injury (AKI), raising concern. METHOD: We report the case of a 73-year-old Caucasian woman admitted for hyperthermia and digestive disorders. She had recently started a first-line chemotherapy for multiple myeloma with partial response. She also displayed preexisting stage 4 CKD (eGFR 18.50 mL/min/1.73 m2 using CKD-EPI) of unknown aetiology. She was tested positive for SARS-CoV2 by nasopharyngeal swab and soon transferred to the intensive care unit. She received intravenous corticosteroids using dexamethasone 6 g/24 h for 10 days and a piperacillin + tazobactam probabilistic antibiotherapy. She also received high doses (15 g/24 h) of vitamin C for three consecutive days. No monoclonal antibodies were prescribed due to a previous vaccination with a positive serology upon admission. Although the patient recovered from respiratory tract infection, her kidney function progressively deteriorated with serum creatinine levels rising up to 8.06 g/dL, leading to her admission in our nephrology department. The patient was initially treated with high doses of diuretics for anasarca and an abdominal CT excluded urinary tract obstruction with normal kidney size and aspect. Urinary analysis showed protein to creatinine (p/c) ratio of 1348 g/g, and presence of urinary light chains. Her monoclonal spike was measured at 2.3 g/L and her kappa/lambda fraction was 1.74. Intermittent haemodialysis was initiated, and a kidney biopsy was performed. RESULTS: Histology revealed hundreds of intratubular calcium oxalate crystals, with severe and diffuse acute tubular necrosis and interstitial edema. There was no amyloidosis, no sign of active glomerular disease and no interstitial fibrosis. Immunofluorescence (IgA, IgG, IgM, C1Q, C3, kappa and lambda) was negative. We concluded to oxalate nephropathy. After a 2-month follow-up, the patient remains dialysis dependent. Vitamin C is a precursor of oxalate and has been shown to cause secondary oxaluria, particularly with high-dose regimens in patients with altered renal function. Given the histological findings evocative of acute oxalate nephropathy, the accountability of high doses of vitamin C should be considered. No other cause of hyperoxaluria was identified in our patient beside broad spectrum antibiotic use, which could decrease intestinal bacterial oxalate degradation. In particular, there was no malabsorption The limitation of our report is the unknown cause of preexisting CKD;therefore, we cannot rule out preexisting hyperoxaluria. Also, no dosage of serum vitamin C and oxalate levels were performed during follow-up. Finally, our patient had other possible causes AKI, such as recent SARS-CoV2 infection, or linked to multiple myeloma, but these were considered unlikely given the proper haematological response to treatment and non-evocative biopsy. The rationale for vitamin C use in COVID-19 is based on in vitro studies showing its antioxidant, anti-inflammatory, anticoagulant and immune modulatory properties. There lack large clinical studies, and the literature shows conflicting results. Multiple cases of acute oxalate nephropathy were described. CONCLUSION: Vitamin C is an anti-inflammatory treatment used in COVID-19 that can lead to secondary hyperoxaluria with significant and irreversible AKI. Due to the severity of AKI in patients with preexisting CKD, we believe renal function should be considered before using high doses of vitamin C. Larger controlled trials are needed both to establish the clinical benefit of vitamin C and further describe its potential ephrotoxicity.

SHOULD WE BE TESTING FOR SPIROCHETOSIS IN COVID PATIENTS PRESENTING WITH PERSISTENT DIARRHEA? A CASE STUDY

Purpose/Background: In the US, intestinal spirochetosis (IS) as a cause of infectious colitis has mainly been described in the HIV positive population. This case describes IS in an HIV negative, COVID positive patient suggesting the need for a broader differential of chronic diarrhea in the COVID era. Hypothesis/Aim: To increase awareness of the need for a potentially broader differential of chronic diarrhea in the COVID era. Methods/Interventions: This is a case study describing an association between COVID and intestinal spirochetosis. Results/Outcome(s): Spirochetes, gram negative spiral-shaped flagellated bacteria, are best known for their ability to cause systemic disease in the form of Syphilis and Lyme Disease, but the genus Brachyspiraceae (Brachyspira aalborgi, Brachyspira pilosicoli) has also been described as both a commensal organism and an invasive pathogen causing intestinal spirochetosis (IS). IS in the US has largely been described in the MSM HIV population as a colitis presenting with abdominal pain and persistent diarrhea secondary to epithelial invasion with destruction of the intestinal brush border leading to malabsorption. IS remains an important part of the work up of infectious colitis in this population. In this case study, IS was diagnosed in an HIV negative, COVID positive patient whose COVID diagnosis coincided with the symptomatic presentation of IS suggesting that it is important to include IS in the differential diagnosis of chronic diarrhea in the COVID population regardless of HIV status. In this study, a 60 yo HIV negative MSM presented with abdominal pain x 3 weeks followed by persistent watery diarrhea refractory to imodium. No history of recent travel. No known infectious contacts. Prior colonoscopy 9 years prior to presentation WNL. After one episode of hematochezia, CT abd/pelvis was performed demonstrating colitis and COVID-related changes to the lung bases. Testing confirmed COVID infection, which was self-limited. Initial work up for infectious colitis was negative for gonorrhea, chlamydia, HIV, HSV, O+P, and C. Difficile. Colonoscopy was performed revealing no evidence of gross colitis. Histopathology demonstrated microscopic colitis w/ spirochete colonization of the intestinal epithelium (image 1). A course of metronidazole led to resolution of symptoms. Limitations: This is a descriptive study describing an association, but it does not imply causation. Conclusions/Discussion: Intestinal spirochetosis has been described as a cause of abdominal pain and refractory diarrhea in the US mainly in an immunosuppressed, HIV positive population. This case describes symptomatic intestinal spirochetosis in an HIV negative, COVID positive patient who hitherto COVID diagnosis had no risk factors for immunosuppression suggesting a link between COVID and IS. Further review is necessary to establish a true association, but this case suggests that IS should be considered during the work up of chronic diarrhea in COVID positive patients. (Figure Presented).

Lactose tolerance test as an alternative to hydrogen breath test in the study of lactose malabsorption.

Objectives: Lactose malabsorption is generally assessed by hydrogen breath testing (HBT). However, this test is not recommended in patients with high baseline hydrogen concentrations (H2B). In addition, breath testing is not recommended in the current situation created by the COVID-19 pandemic, due to the potential infectiveness of the samples. The objective is to assess concordance between HBT and lactose tolerance test (LTT) depending on H2B concentrations. Methods: A total of 430 patients (40 years, Q1-Q3 = 28-54 years; 66.7% women) suspected of lactose malabsorption were included in the study. Breath and heparinized blood samples were collected at baseline and sequentially after the intake of 50 g of lactose, to measure hydrogen in breath and glycemia in blood, respectively. Results: H2B was <10 ppm in 69.5% of subjects; 10-20 ppm in 14.7%; and >20 ppm in 15.8% of subjects. In patients with H2B <20 ppm, concordance between HBT and LTT was moderate and consistently improved when the cut-off in LTT was set at 15 mg/dL. The increase in hydrogen and glucose correlated negatively (r=-0.389; p<0.05). The increase in glycemia during LTT was not influenced by H2B levels obtained in HBT. Conclusions: LTT emerges as an alternative to HBT to assess lactose malabsorption in the presence of high H2B levels or when breath testing is not recommended by the circumstances. The best concordance was obtained when the cut-off for LTT was set at 15 mg/dL.

Hypovitaminosisd on an adult female: From autoimmune conditions to pandemic days

Objective: COVID-19 pandemic was associated with increased risk of hypovitaminosis D due to lockdown regulations and limited outdoor activities, while young adult patients with autoimmune conditions may associated decreased values of 25-hydroxyvitamin D due to copresence of celiac disease, glucocorticoid exposure, malabsorption, overtreatment of autoimmune hypothyroidism, etc. (1-5).We aim to introduce a female case known with autoimmune conditions who was admitted for vitaminD deficiency related symptoms during pandemic. Case report: A 41-year-old, nonsmoker female is admitted for nonspecific muscle cramps, and joints pain, asthenia which is persistent for the last several months in addition to chronic low back pain (which required chronic use of nonsteroid anti-inflammatory medication). Her personal medical background reveals a diagnosis of HLA-B27-positive ankylosing spondylitis that was established seven years before current admission. She is also known with autoimmune thyroiditis with negative antibodies, a diagnostic that was based on suggestive ultrasound features with highly hypoechoic pattern of relative small thyroid gland (and normal thyroid function). She is also confirmed with thrombophilia. She has a negative personal history of confirmed COVID-19 infection and she followed the lockdown restrictions for several weeks. The family medical history is irrelevant. On admission, clinical examination of the thyroid is within normal limits on amenstruated normal weighted female. Biochemistry data points out normal total calcium of 9.45 mg/dL (normal: 8.4-10.3 mg/dL). Endocrine panel shows TSH=1.28 μUI/mL (normal: 0.5-4.5 μUI/mL), free levothyroxine=11.65 pmol/L (normal: 9-19 pmol/L), anti-thyroperoxidase antibodies=10.88 UI/mL (normal: 0-35), anti-thyroglobulin antibodies=10 UI/mL (normal: 0-115 UI/mL). 25-hydroxyvitamin D=10 ng/mL (normal >30 ng/mL) with increased PTH levels and negative antibodies for celiac disease. Supplementation with daily 2000 UI of vitamin D for 12 weeks followed by daily 1000 UI was recommended. Conclusion: The association thrombophilia-hypovitaminosis D has been reported in some patients, but it is rather incidental. Chronic use of antiinflammatory medication may cause malabsorption, and also the potential of a second autoimmune disease at intestinal level may cause this deficiency, but the current pandemic reality has become a new cause of it.

Altered tryptophan absorption and metabolism could underlie long-term symptoms in survivors of coronavirus disease 2019 (COVID-19).

The global pandemic of COVID-19 has been lasting for more than one year and there is little known about the long-term health effects of the disease. Long-COVID is a new term that is used to describe the enduring symptoms of COVID-19 survivors. Huang et al. reported that fatigue, muscle weakness, sleep disturbances, anxiety, and depression were the most common complaints in COVID-19 survivors after 6 months of the infection. A recent meta-analysis showed that 80% of COVID-19 survivors have developed at least one long-term symptom and the most common five were fatigue, headache, attention deficit disorder, hair loss, and dyspnea. In this paper, we discuss the hypothesis that altered tryptophan absorption and metabolism could be the main contributor to the long-term symptoms in COVID-19 survivors.

An examination of gastrointestinal absorption using the acetaminophen absorption test in critically ill patients with COVID-19: A retrospective cohort study.

OBJECTIVE: Gastrointestinal (GI) dysfunction is prevalent in critically ill patients with coronavirus disease 2019 (COVID-19). The acetaminophen absorption test (AAT) has been previously described as a direct method for assessment of GI function. Our study determines whether the AAT can be used to assess GI function in critically ill COVID-19 patients, compared with traditional measures of GI function. DESIGN: Retrospective observational study of critically ill patients with COVID-19. SETTING: Three intensive care units at a tertiary care academic medical center. PATIENTS: Twenty critically ill patients with COVID-19. INTERVENTIONS: The results of AAT and traditional measures for assessing GI function were collected and compared. MEASUREMENTS AND MAIN RESULTS: Among the study cohort, 55% (11 of 20) of patients had evidence of malabsorption by AAT. Interestingly, all patients with evidence of malabsorption by AAT had clinical evidence of bowel function, as indicated by stool output and low gastric residuals during the prior 24 h. When comparing patients with a detectable acetaminophen level (positive AAT) with those who had undetectable acetaminophen levels (negative AAT), radiologic evidence of ileus was less frequent (20 vs 88%; P = .03), tolerated tube-feed rates were higher (40 vs 10 ml/h; P =.01), and there was a trend toward lower gastric residual volumes (45 vs 830 ml; P =.11). CONCLUSION: Malabsorption can occur in critically ill patients with COVID-19 despite commonly used clinical indicators of tube-feeding tolerance. The AAT provides a simple, rapid, and cost-effective mechanism by which enteral function can be efficiently assessed in COVID-19 patients.