Bittersweet: infective complications of drug-induced glycosuria in patients with diabetes mellitus on SGLT2-inhibitors: two case reports

Abstract Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel hypoglycemic agents which reduce reabsorption of glucose at the renal proximal tubule, resulting in significant glycosuria and increased risk of genital mycotic infections (GMI). These infections are typically not severe as reported in large systematic reviews and meta-analyses of the medications. These reviews have also demonstrated significant cardiovascular benefits through other mechanisms of action, making them attractive options for the management of Type 2 diabetes mellitus (T2DM). We present two cases with underlying abnormalities of the urogenital tract in which the GMI were complicated and necessitated cessation of the SGLT2 inhibitor. Case presentations Both cases are patients with T2DM on empagliflozin, an SGLT2 inhibitor. The first case is a 64 year old man with Candida albicans balanitis and candidemia who was found to have an obstructing renal calculus and prostatic abscess requiring operative management. The second case describes a 72 year old man with Candida glabrata candidemia who was found to have prostatomegaly, balanitis xerotica obliterans with significant urethral stricture and bladder diverticulae. His treatment was more complex due to fluconazole resistance and concerns about urinary tract penetration of other antifungals. Both patients recovered following prolonged courses of antifungal therapy and in both cases the SGLT2 inhibitor was ceased. Conclusions Despite their cardiovascular benefits, SGLT2 inhibitors can be associated with complicated fungal infections including candidemia and patients with anatomical abnormalities of the urogenital tract may be more susceptible to these infections as demonstrated in these cases. Clinicians should be aware of their mechanism of action and associated risk of infection and prior to prescription, assessment of urogenital anatomical abnormalities should be performed to identify patients who may be at risk of complicated infection.

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Cerebral venous thrombosis secondary to an occult maxillary sinusitis in a young male from sub-Saharan Africa

10.36811/ojor.2019.110002 ◽

2019 ◽

pp. 08-12

Author(s):

Mazou N Temgoua ◽

Mickael Essouma ◽

Larry N Tangie ◽

Cedric Tsinda ◽

Drusille Feze Foko ◽

...

Keyword(s):

Venous Thrombosis ◽

Acute Stroke ◽

Cerebral Venous Thrombosis ◽

Fungal Infections ◽

Sinus Thrombosis ◽

Maxillary Sinusitis ◽

Case Reports ◽

Sub Saharan Africa ◽

First Case ◽

Increased Risk

Cerebral venous thrombosis (CVT) also termed cerebral venous sinus thrombosis (CVST), is a special type of cerebrovascular disease characterized by cerebral venous infarction [1]. As from 1825 when the first case was described by Ribes[2], epidemiological descriptions are still restricted to case reports and small retrospective cross-sectional studies yielding low butincreasing incidence: <10 cases per million per year in 1995 to about 13.2 cases per million per year in 2012.CVT mainly occurs in women of child bearing age, probably owing to the use of oral contraceptive pills, and mostly has an acute or subacute course [1]. It can be categorized as primary/idiopathicand secondary. Secondary CVT can further be classified into infective (mainly due to bacterial or fungal infections) and non-infective CVT; the latterbeing due tocoagulation disorders, neoplasms, procoagulant hemodynamic states, vascularitis,homocystinuria, or head trauma [3].With the advent of antibiotics, the epidemiology of CVT has shifted from predominant infective CVT to predominant non-infective CVT, leading to increased risk of misdiagnosis and delayed treatment [3]. We report occult purulent maxillary sinusitis-related CVT in a male Cameroonian patient who presented with headaches, seizures and acute stroke syndrome. The aim of this paper is to reiterate CVT as the main cause of acute stroke syndrome in young adults irrespective of ethnic origin and sex, and suggest systematic screening of infections in those patients, especially in regions with high rates of infections likesub-Saharan Africa.We describe this case with regard to CARE guidelines.

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Safety of SGLT2 Inhibitors in Patients with Diabetes Mellitus

Current Drug Safety ◽

10.2174/1574886314666190206164647 ◽

2019 ◽

Vol 14 (2) ◽

pp. 87-93 ◽

Cited By ~ 7

Author(s):

Mahakpreet Singh ◽

Ruchika Sharma ◽

Anoop Kumar

Keyword(s):

Diabetes Mellitus ◽

Urinary Tract Infection ◽

Urinary Tract ◽

Tract Infection ◽

Diabetic Ketoacidosis ◽

Adverse Drug Reactions ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Drug Reactions ◽

Authorization Holder

Background:Recently, Food and Drug Administration (FDA) has approved sodium/ glucose co-transporter 2 (SGLT2) inhibitors for the treatment of diabetes mellitus. However, regarding adverse drug reactions (ADRs) of SGLT2 inhibitors in large group of population, very less information is available. Thus, we have tried to find out the risk profile of SGLT2 inhibitors. Materials and Methods: A total of 1,042 studies have been published from Nov. 2012-Nov. 2017 regarding SGLT2 inhibitors. After inclusion and exclusion criteria, 27 studies have been selected for the analysis of risk. Results and Discussion:The emerging evidence indicates various adverse drug reactions such as foot and toe amputation, cancer, diabetic ketoacidosis, bone fracture risk and urinary as well as mycotic genital infection. The causality assessment has shown a correlation between SGLT2 inhibitors and diabetic ketoacidosis and urinary tract infection. Conclusion:In conclusion, Marketing Authorization Holder (MAH) and Regulatory Authorities (RA) should monitor various adverse drug reactions such as diabetic ketoacidosis and urinary tract infection with the use of SGLT2 inhibitor.

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Nephrolithiasis against type 2 diabetes mellitus: on the effect of hypoglycemic therapy on lithogenesis

Terapevticheskii arkhiv ◽

10.26442/terarkh201890104-64 ◽

2018 ◽

Vol 90 (10) ◽

pp. 60-64

Author(s):

S K Yarovoy ◽

E N Kareva ◽

O V Djalilov

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Negative Impact ◽

Stone Formation ◽

Hypoglycemic Agents ◽

Control Group ◽

City Hospital ◽

Increased Risk

Aim. To study the effects of oral hypoglycemic agents that can affect the probability of recurrence of nephrolithiasis. Materials and methods. The article is based on the results of examination and treatment of 315 patients suffering from recurrent nephrolithiasis and medically compensated type 2 diabetes mellitus treated at the N.A. Lopatkin Institute of Urology and Interventional Radiology - the branch of the SMRC of Radiology, Ministry of Health of Russia and D.D. Pletnev City Hospital Moscow Healthcare Department in 2012-2017. The patients were divided into three groups according to the applied tool antidiabetic: metformin, glibenclamide, canagliflozin. The control group consisted of patients receiving insulin therapy. Results and discussion. The propensity of Metformin to reduce the pH of urine, which has a negative impact in the conditions of urate nephrolithiasis, which is most common in the population of patients with type 2 diabetes mellitus. Glibenclamide, on the contrary, somewhat latches urine. But changes in the reaction of urine under the influence of the drug do not go beyond normal values and are not clinically significant. Canagliflozin increases diuresis due to medication induced glycosuria and stimulates renal excretion of uric acid and its salts. However canagliflozin does not cause significant shifts in the pH of urine that may somewhat negates the increased risk of recurrence of urate stone formation in the background of the uricosuric effect of the drug. Conclusion. Drug therapy of type 2 diabetes mellitus significantly affects the properties of urine from patients with nephrolithiasis.

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Euglycemic Diabetic Ketoacidosis Associated With Sodium–Glucose Cotransporter Type 2 Inhibitors in Patients With Type 2 Diabetes Mellitus Receiving Oral Therapy

Journal of Pharmacy Practice ◽

10.1177/0897190017748049 ◽

2017 ◽

Vol 32 (2) ◽

pp. 240-243 ◽

Cited By ~ 3

Author(s):

Ryan B. Dull ◽

Mikayla L. Spangler ◽

Emily L. Knezevich ◽

Britney M. Lau

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Diabetic Ketoacidosis ◽

Case Reports ◽

Serious Adverse Events ◽

Type 2 Dm ◽

Sodium Glucose Cotransporter ◽

Increased Risk

Introduction and Objective: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium–glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. Case Reports: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin. This case was notable for a delayed diagnosis of euDKA and lack of clinical improvement despite withholding dapagliflozin. Subject 2 is a 62-year-old male admitted with euDKA precipitated by infection. His clinical condition improved rapidly and euDKA responded to withdrawal of empagliflozin alone. Discussion: Applying the Naranjo adverse medication reaction probability scale to each case (subject 1 score = 3 points; subject 2 score = 4 points) suggests these are possible adverse reactions to SGLT2i. Data from randomized controlled trials suggest DKA events in adults with type 2 DM receiving SGLT2i are rare and similar to placebo. However, data from a large cohort suggest these events occur more frequently and are associated with a 2-fold increased risk of DKA. Conclusion: This class of medications may be associated with a higher real-world risk of DKA in adults with type 2 DM than previously reported. Patients prescribed these medications should receive vigilant assessment for features of traditional DKA as well as euDKA.

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Assessment of Candidal carriage in patients with Type II Diabetes Mellitus

Journal of Pathology of Nepal ◽

10.3126/jpn.v5i9.13784 ◽

2015 ◽

Vol 5 (9) ◽

pp. 733-738 ◽

Cited By ~ 2

Author(s):

RS Lamichhane ◽

K Boaz ◽

S Natarajan ◽

M Shrestha

Keyword(s):

Diabetes Mellitus ◽

Fungal Infections ◽

Surrogate Marker ◽

Salivary Flow ◽

Type Ii Diabetes Mellitus ◽

Serum Glucose ◽

Denture Stomatitis ◽

Oral Rinse ◽

Increased Risk ◽

Patients With Diabetes

Background: It is generally acknowledged that patients with diabetes mellitus are more susceptible to fungal infections, particularly with Candida albicans. Oral infection by Candida can result in a number of clinical lesions, including median rhomboid glossitis (central papillary atrophy), denture stomatitis, squamous cell carcinoma, Radiation therapy, immunocompromised status, etc. Different studies have shown that patients with diabetes mellitus have increased frequency of oral candidal carriage and increased risk of candidiasis, which is related to poor metabolic control, neutrophil dysfunction, reduced salivary flow, high glucose concentration in blood and saliva and in medications.Materials and Methods: Subjects of both the groups were given 10 ml of sterile normal saline and asked to rinse the mouth for one minute. The subjects were then asked to return the oral rinse in a sterile clean, broad-mouthed container which was capped, labelled and taken to the laboratory. The samples were then inoculated onto the culture medium (Sabouraud’s dextrose agar with Chloramphenicol) with minimal delay (within 6-8 hours of collection of oral rinse). Candidal colonies were counted and compared with non-diabetics.Results: Statistically significant increase in colony forming units (p=0.0324) were obtainedin patients with diabetes mellitus.Conclusion: The results indicate significant increase in colonization and carriage of candida in the oral cavity among diabetics when compared with non-diabetics. However, further research using larger samples is required which may lend credibility to the suggestion of increased candidal CFUs in diabetics serving as a surrogate marker of serum glucose levels.Journal of Pathology of Nepal (2015) Vol. 5, 733-738

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Case Reports That Illustrate the Efficacy of SGLT2 Inhibitors in the Type 1 Diabetic Patient

Case Reports in Endocrinology ◽

10.1155/2015/676191 ◽

2015 ◽

Vol 2015 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

David S. H. Bell

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Case Reports ◽

Sglt2 Inhibitor ◽

Sglt2 Inhibitors ◽

Endogenous Insulin ◽

Large Randomized Clinical Trial ◽

Endogenous Insulin Production

SGLT2 inhibitors are only approved for use in adults with type 2 diabetes. However, because SGLT2 inhibitors have a mechanism of action that does not require the presence of endogenous insulin, these drugs should also be efficacious in type 1 diabetes where endogenous insulin production is greatly reduced or absent. Herein, I present five cases which illustrate the benefits of utilizing an SGLT2 inhibitor with type 1 diabetes. In these cases the use of SGLT2 inhibitors resulted not only in better glycemic control in most patients but also in some patients’ less hypoglycemia, weight loss, and decreased doses of insulin. In type 1 diabetesCandida albicansvaginitis and balanitis may occur more frequently than in type 2 diabetes. These cases show that a large randomized clinical trial of SGLT2 inhibitors in type 1 diabetes needs to be performed.

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Burning Mouth Syndrome: Problem in the Mouth?

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.049 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S254-S254

Author(s):

S. Petrykiv ◽

L. de Jonge ◽

M. Arts

Keyword(s):

Case Report ◽

Case Reports ◽

Antidepressant Medication ◽

Burning Mouth Syndrome ◽

Psychiatric Ward ◽

Drug Induced ◽

First Case ◽

Painful Sensation ◽

Burning Mouth ◽

Competing Interest

IntroductionBurning mouth syndrome (BMS) is characterized by an intraoral burning sensation for which no medical or dental cause can be found. Sporadic evidence suggests that drug induced conditions may evoke BMS. Intriguingly, we observed a patient who developed BMS after induction of citalopram.Objectives & aimsA case report of patient with BMS from our psychiatric ward will be presented here, followed by a literature review on drugs induced BMS.MethodsBased on a recent literature search, we present a first case report of BMS that was apparently induced in patient shortly after beginning of citalopram. We performed a systematic search through PubMed, EMBASE and Cochrane's Library to find more cases of psychotropic induced BMS.ResultsMs. A. was a 72-year old woman meeting DSM-IV diagnostic criteria for melancholic depression, who was observed in a clinical setting. We started citalopram 10 mg. 1dd1, with 10 mg. 1dd1 increase over 7 days to 20 mg, 1dd1. The following day, she displayed a persistent burning painful sensation in the mouth. Other than BMS oropharyngological syndromes were excluded after consultation with qualified medical specialists. Citalopram therapy was discontinued, and nortrilen treatment was initiated. BMS symptoms resolved over four days. Twelve case reports have linked BMS to the use antidepressants and anxiolytics.ConclusionContrasting the statement that no medical cause can be found for BMS, we found that psychotropics may evoke the syndrome. Compared to other psychotropic drugs, antidepressant medication has the strongest association with BMS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Recurrent Ameloblastoma: A Surgical Challenge

Case Reports in Dentistry ◽

10.1155/2018/8271205 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6

Author(s):

Chithra Aramanadka ◽

Abhay Taranath Kamath ◽

Adarsh Kudva

Keyword(s):

Frozen Section ◽

Case Reports ◽

Infratemporal Fossa ◽

Histologic Subtype ◽

Holistic Management ◽

First Case ◽

Increased Risk ◽

Choice Of Treatment ◽

Radical Therapy ◽

Intraoperative Radiography

Ameloblastoma is locally aggressive benign odontogenic tumour with increased risk of recurrence rate. The choice of treatment depends on the histologic subtype. Radical therapy is the recommended modality for solid ameloblastomas. The possibilities of recurrence even after enbloc resection are still high. The author presents two case reports of recurrent ameloblastomas postradical resection. First case describes the recurrence of ameloblastoma in the bone graft which was used for reconstruction, and the second case depicts recurrence in the infratemporal fossa. Intraoperative radiography of the frozen section of the soft tissue margin plays an important role in the holistic management of these lesions.

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Lichen Planus Pemphigoides Induced by Enalapril: A Case Report and a Review of Literature

Case Reports in Dermatology ◽

10.1159/000481449 ◽

2017 ◽

Vol 9 (3) ◽

pp. 217-224 ◽

Cited By ~ 5

Author(s):

Woranit Onprasert ◽

Kumutnart Chanprapaph

Keyword(s):

Lichen Planus ◽

Early Recognition ◽

Case Reports ◽

Direct Immunofluorescence ◽

Drug Induced ◽

First Case ◽

Bullous Dermatosis ◽

Culprit Drug ◽

History Of ◽

Hands And Feet

Lichen planus pemphigoides (LPP) is a rare autoimmune bullous dermatosis. The clinical presentation of LPP may mimic bullous pemphigoid making the diagnosis difficult. A thorough clinical, histopathological, and immunological evaluation is essential for the diagnosis of LPP. The etiology is largely idiopathic; however, there are several case reports of drug-induced LPP. We report an 81-year-old Thai woman with underlying hypertension and type 2 diabetes mellitus who presented with a 4-week history of multiple tense bullae initially on the hands and feet that subsequently expanded to the trunk and face. Enalapril was commenced to control hypertension. The histopathology and direct immunofluorescence were compatible with LPP. Circulating anti-basement antibodies BP180 was also positive. The patient was treated with topical corticosteroid with a modest effect. Enalapril was discontinued and complete resolution of LPP occurred within 12 weeks. There was no recurrence after a 1-year follow-up period. To the best of our knowledge, we present the first case of enalapril-induced LPP. Early recognition and prompt discontinuation of the culprit drug allow resolution of the disease. Medication given for LPP alone, without cessation of the offending drug, may not change the course of this condition.

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Dementia-Like Symptoms Associated With Posaconazole

Journal of Pharmacy Practice ◽

10.1177/0897190020958235 ◽

2020 ◽

pp. 089719002095823

Author(s):

Carmela E. Corallo ◽

Steven P. Ivulich ◽

Dr Sakhee Kotecha ◽

Orla Morrissey

Keyword(s):

Lung Transplant ◽

Fungal Infections ◽

Transplant Recipients ◽

First Case ◽

Increased Risk ◽

Post Marketing ◽

Scedosporium Prolificans ◽

Lung Transplant Recipients ◽

Dose Dependent

Posaconazole is widely used in lung transplant recipients as pre-emptive therapy or universal fungal prophylaxis. In this patient group, posaconazole is increasingly used instead of voriconazole due to the concerns of an increased risk of squamous cell carcinoma (SCC) with voriconazole, particularly with its long-term use. Dose dependent toxicity has not been identified for posaconazole in the registration trials of intravenous (IV) and modified-release tablet formulations. This is supported by post-marketing experience. We describe a lung transplant recipient who experienced dementia-like symptoms almost 3 years after commencing posaconazole for treatment of Aspergillus fumigatus complex and Lomentospora prolificans (formerly Scedosporium prolificans) fungal infections. Symptoms resolved upon discontinuation of posaconazole, but recurred when re-challenged at a lower dose more than a year later. To the best of our knowledge, this is the first case reporting a dementia-like state with posaconazole.

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