General malaise, arthralgias, skin rash, acute renal failure and active sediment with sterile leukocyturia following the intake of a drug is highly suggestive of AIN (option 4 correct). Among drugs, antibiotics are the most frequent cause, and ciprofloxacin is one of the most common. Direct nephrotoxicity is very rare and is characterized by crystallization in the renal tubules (incorrect option 2). Postinfectious glomerulonephritis is more typical of children and adults older than 60 years, and usually manifests with hematuria after streptococcal infections (option 1 incorrect). Acute pyelonephritis would have been presented with high fever and renal fossa pain (option 3 incorrect).

General malaise, arthralgias, skin rash, acute renal failure and active sediment with sterile leukocyturia following the intake of a drug is highly suggestive of AIN ([HIDDEN]). Among drugs, antibiotics are the most frequent cause, and ciprofloxacin is one of the most common. Direct nephrotoxicity is very rare and is characterized by crystallization in the renal tubules ([HIDDEN]). Postinfectious glomerulonephritis is more typical of children and adults older than 60 years, and usually manifests with hematuria after streptococcal infections ([HIDDEN]). Acute pyelonephritis would have been presented with high fever and renal fossa pain ([HIDDEN]).

A 47-year-old woman consults for voiding syndrome. She is diagnosed with uncomplicated urinary tract infection and treated with ciprofloxacin for 5 days. A week later, she consulted again for general malaise, arthralgias and the appearance of a skin rash. In the analytical analysis, the glomerular filtration rate was 45 ml/min (CKD-EPI), whereas 6 months ago it was 100 ml/min. In the sediment leukocytes are identified, being negative for nitrites. Of the following, which is the most probable cause of his renal failure?

Is ciprofloxacin safe in patients with solitary kidney and upper urinary tract infection?

The solitary kidney (SK) undergoes adaptive phenomena of hyperfunction and hyperfiltration. These secondary adaptive phenomena can make it more vulnerable to potentially nephrotoxic therapies. Adverse reactions of the kidneys to ciprofloxacin are rare, but sometimes severe. Therefore, our study sought to assess the reactions to ciprofloxacin of patients with solitary kidney (SK) and urinary tract infection (UTI) by means of urinary biomarkers. We studied 19 patients with SK and urinary tract infection (UTI) who had been administered a 7-day treatment with intravenous ciprofloxacin. Urinary N-acetyl-beta-d-glucosaminidase, alpha 1-microglobulin, and estimated glomerular filtration rate (eGFR) of these patients were measured at the initiation and at the end of treatment. In 47.37% patients NAG diminished under ciprofloxacin treatment. This observation has the significance of favourable evolution of the tubulointerstitial lesions caused by UTI and lack of nephrotoxic effects; 52.63% cases presented an increase of urinary NAG, a fact that suggests a nephrotoxic effect of ciprofloxacin. The evolution of urinary alpha 1-microglobulin was similar to that one of urinary NAG. Only one of three cases with chronic kidney disease (CKD) stage 5 presented acute kidney injury, associated with increase in the tubular markers. In spite of the high variability of the urinary biomarkers, UTI evolved favourably in these cases; eGFR increased in 16 out of 19 patients, a fact which is indicative of a good outcome of renal function, even in patients with elevated levels of the tubular damage biomarkers. This observation supports the hypothesis that eGFR may be dissociated from the biomarkers which assess tubular injury. In SK patients the occurrence of AKI is not frequent, although the urinary biomarkers rise in some patients treated with ciprofloxacin. This is related not only to the nephrotoxic effect of the drug, but probably to the association of other factors (allergy, individual susceptibility). In SK patients, renal tubular biomarkers, especially NAG, allow monitoring of tubular injury and impose caution in prescribing ciprofloxacin treatment, mainly to patients at risk. Ciprofloxacin is relatively safe regarding its nephrotoxicity, while caution is required in vulnerable patients.

[Unexpected cause of acute renal failure in an 85-year-old woman].

Acute postinfectious glomerulonephritis (APIGN) is usually diagnosed in young people, while in elderly people rapidly progressive forms appear to be the most important glomerular disease causing acute renal failure. We report on a 85-year-old woman with acute renal failure due to APIGN. An 85-year-old woman with a history of hypertension and cerebrovascular disease was hospitalized because of diarrhea and syncope associated with atrial fibrillation. She was found to have left lower lobe pneumonia. Serum creatinine was over 2 mg/dL. Fluids were given, without improvement in renal function but leading to volume overload instead. Within a few days serum creatinine reached a level of 5.4 mg/dL with reduction of urine output despite administration of diuretics. The patient developed hematuria and purpura of the feet. Serum IgA was high and the urine sediment showed casts. Methylprednisolone 125 mg i.v. was given for three days followed by prednisone 50 mg daily. The patient's clinical condition gradually improved and serum creatinine decreased to 1.9 mg/dL. Renal biopsy showed APIGN. During hospitalization, three major complications occurred: hemodynamic instability due to atrial fibrillation, Clostridium difficile colitis and urinary tract infections due to Enterococcus faecalis and Candida tropicans, all successfully treated. APIGN should be taken into account as a cause of acute renal failure in hospitalized elderly patients with many comorbidities.

Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women.

The antibiotic nitrofurantoin is commonly used to treat uncomplicated urinary tract infections. However, when this drug is used by patients with reduced kidney function, its urine concentration may be subtherapeutic. We conducted a population-based study of older women (mean age 79 years) in Ontario, Canada, whose estimated glomerular filtration rate was relatively low (median 38 mL/min per 1.73 m(2)) and for whom 1 of 4 antibiotics had been prescribed for urinary tract infection: nitrofurantoin, ciprofloxacin, norfloxacin or trimethoprim-sulfamethoxazole. We assessed 2 measures of treatment failure in the subsequent 14 days: receipt of a second antibiotic indicated for urinary tract infection and hospital encounter (emergency department visit or hospital admission) with a urinary tract infection. We repeated the analysis for older women with relatively high estimated glomerular filtration rate (median 69 mL/min per 1.73 m(2)). The baseline characteristics of the 4 antibiotic groups were similar. Relative to nitrofurantoin, the other antibiotics (including ciprofloxacin) were associated with a lower rate of treatment failure among women with relatively low estimated glomerular filtration rate (for ciprofloxacin v. nitrofurantoin: second antibiotic prescription, 130/1989 [6.5%] v. 516/3739 [13.8%], odds ratio [OR] 0.44, 95% confidence interval [CI] 0.36-0.53; hospital encounter, 21/1989 [1.1%] v. 95/3739 [2.5%], OR 0.41, 95% CI 0.25-0.66). However, a similar risk of treatment failure with nitrofurantoin was also observed among women with relatively high estimated glomerular filtration rate. The results were consistent in multiple additional analyses. In this study, the presence of mild or moderate reductions in estimated glomerular filtration rate did not justify avoidance of nitrofurantoin.

Ten Cases of Biopsy-Proven Acute Tubulointerstitial Nephritis: Report from a Single Center in a Rural Area from 2008 to 2021.

Acute tubulointerstitial nephritis (ATIN) can be caused by any number of factors, and it accounts for several percent of renal biopsy cases. In Japan, case reports exist, but there are few single-center series of ATIN cases. <iCase 1</i. A teenage male patient developed fever and cough on day X-61 and was found to have normal renal function and positive C-reactive protein (CRP) by his primary care physician. On day X-20, he presented with cough and nasal discharge in addition to low-grade fever, and his doctor noted renal dysfunction with serum creatinine of 2.12 mg/dL, negative urine occult blood, and positive urine glucose. Renal biopsy results showed diffuse interstitial nephritis with scarce glomerular involvement. There was no concurrent uveitis. Renal function normalized after 4 months of treatment with moderate-dose prednisolone. <iCases 2-10</i. Of the 422 cases for which renal biopsies were performed at our institution from 2008 to 2021, acute tubulointerstitial nephritis was confirmed clinically and pathologically in 9 cases in addition to case 1, accounting for 2.4% of all biopsy cases. In the analysis of the 10 patients, the median age was 40 years old, eGFR at diagnosis was 19.4 (3.2-49.1) mL/min/1.73 m<sup2</sup, and 2 of them underwent hemodialysis, but both were weaned from dialysis, and the eGFR after treatment was 53.6 (20.8-110.0) mL/min/1.73 m<sup2</sup; all patients showed improvement (<iP</i < 0.001). Treatment consisted of steroids in 8 patients and no steroids in 2 patients, the latter being treated by discontinuation of the suspect drugs and treatment of infection; 7 of the 10 patients were examined for ocular uveitis, and uveitis was diagnosed in 5 patients. The causes and clinical course of ATIN are diverse, but it is treated according to individual judgment in addition to standard treatment, and it generally has a good renal prognosis.

List of MeSH codes (C12)

– anti-glomerular basement membrane disease – goodpasture syndrome – glomerulonephritis, iga – glomerulonephritis, membranoproliferative – glomerulonephritis, membranous – glomerulosclerosis, focal – lupus nephritis – nephritis, hereditary – nephritis, interstitial – balkan nephropathy – pyelonephritis – pyelonephritis, xanthogranulomatous – nephrocalcinosis – nephrosclerosis – nephrosis – nephrosis, lipoid – nephrotic syndrome – perinephritis – pyelitis – pyelonephritis – pyelonephritis, xanthogranulomatous – renal artery obstruction – renal insufficiency – kidney failure – kidney failure, acute – kidney tubular necrosis, acute – kidney failure, chronic – renal insufficiency, acute – kidney failure, acute – kidney tubular necrosis, acute – renal insufficiency, chronic – kidney failure, chronic – renal osteodystrophy – renal tubular transport, inborn errors – acidosis, renal tubular – aminoaciduria, renal

Urinary tract infection

Pyelonephritis Pyelonephritis is treated more aggressively than a simple bladder infection using either a longer course of oral antibiotics or intravenous antibiotics. Seven days of the oral fluoroquinolone ciprofloxacin is typically used in areas where the resistance rate is less than 10%. If the local resistance rates are greater than 10%, a dose of intravenous ceftriaxone is often prescribed. Trimethoprim/sulfamethoxazole or amoxicillin/clavulanate orally for 14 days is another reasonable option. In those who exhibit more severe symptoms, admission to a hospital for ongoing antibiotics may be needed. Complications such as ureteral obstruction from a kidney stone may be considered if symptoms do not improve following two or three days of treatment. Prognosis With treatment, symptoms generally improve within 36hours. Up to 42% of uncomplicated infections may resolve on their own within a few days or weeks.

[Chronic renal failure: unexpected late sequela of pulmonary tuberculosis after 30 years].

Tuberculosis-related chronic granulomatous tubulointerstitial nephritis (GTN) and chronic renal dysfunction as a consequence of GTN is a rarely seen clinical condition, with a few case reports in the literature. In this report, a case with end stage renal failure as an unexpected late extrapulmonary sequela of tuberculosis has been presented. A 60 years old female patient was admitted to hospital with the complaints of fever, malaise and nausea. Her history revealed that she had pulmonary tuberculosis 30 years ago and received antituberculosis therapy for nine months. The laboratory results on admission were as follows: blood urea nitrogen 90 mg/dl, serum creatinine 9 mg/dl, sodium 116 mEq/L, potassium 6.6 mEq/L, albumine 2.9 g/dl, hemoglobin, 8.4 g/dl, white blood cell count 10.800/mm3, C-reactive protein 187 mg/L and erythrocyte sedimentation rate 110 mm/hour. Urinalysis showed 8.1 g/L protein, 10-12 leukocytes, 1-2 erythrocytes, while 24-hours urinalysis yielded proteinuria with 8 ml/minutes creatinine clearance value. Urine and blood cultures of the patient revealed neither bacteria or mycobacteria. PPD skin test was negative. Acid-resistant bacilli (ARB) were not detected in sequential urine samples obtained on three consecutive days. Since sputum samples could not be obtained, diagnostic procedures for sputum were not performed. Abdomen ultrasonography yielded bilateral edema and grade II echogenity in kidneys. Computed tomography of the chest showed bilateral pulmonary nodules, chronic sequela lesions, pleural scarring and calcifications, as well as minimal interstitial infiltrate. Transthoracic lung biopsy showed chronic inflammation and fibrosis, while amyloid was negative. Renal biopsy showed GTN with central caseified necrosis and granulomas, multinuclear giant cells, tubular atrophy and interstitial fibrosis. Amyloid was negative and ARB were not detected in renal biopsy sample. Definitive diagnosis was achieved by the demonstration of Mycobacterium tuberculosis nucleic acid in kidney biopsy by polymerase chain reaction (PCR). Antituberculosis therapy was not initiated since there were no signs of active tuberculosis. The patient became clinically stable following dialysis and was discharged, however, she has been undergoing hemodialysis three times a week. The aim of this case presentation was to emphasize that renal tuberculosis should be considered in the differential diagnosis of patients with end stage renal failure, especially in countries like Turkey where tuberculosis incidence is high.

[Postinfectious acute glomerulonephritis].

Postinfectious acute glomerulonephritis mostly happens in children aged two to 10 years old. Typically, it follows group A beta-hemolytic streptococcus skin or upper respiratory tract infection. There is a latent period of one to three weeks before nephritic syndrome appears. Microscopic or macroscopic hematuria is always present. Proteinuria and decreased glomerular filtration rate are usually mild. By contrast, salt and water retention can be severe and complicated with hypertension, congestive heart failure or pulmonary edema. Fluid overload must be urgently treated by loop diuretics or renal replacement therapy in the most severe cases.

Glomerular filtration rate

Normal ranges The normal range of GFR, adjusted for body surface area, is 100–130 average 125 mL/min/1.73m2 in men and 90–120 ml/min/1.73m2 in women younger than the age of 40. In children, GFR measured by inulin clearance is 110 mL/min/1.73 m2 until 2 years of age in both sexes, and then it progressively decreases. After age 40, GFR decreases progressively with age, by 0.4–1.2 mL/min per year. Decreased GFR A decreased renal function can be caused by many types of kidney disease. Upon presentation of decreased renal function, it is recommended to perform a history and physical examination, as well as performing a renal ultrasound and a urinalysis. The most relevant items in the history are medications, edema, nocturia, gross hematuria, family history of kidney disease, diabetes and polyuria. The most important items in a physical examination are signs of vasculitis, lupus erythematosus, diabetes, endocarditis and hypertension.

Acute renal failure secondary to oral ciprofloxacin therapy: a presentation of three cases and a review of the literature.

The fluoroquinolones represent a new class of antimicrobial agents with a broad spectrum of activity. We report three cases of acute renal failure following ciprofloxacin in patients without a previous history of renal insufficiency. The average baseline creatinine was 1.1 mg/dl and rose to an average of 4.0 mg/dl during therapy. The length of antecedent ciprofloxacin therapy ranged from several days to several weeks. Other causes of acute renal failure and postobstructive uropathy were excluded. Kidney size was normal-to-increased. Gallium scans were positive in one of two patients studied. Peripheral eosinophilia developed in one case, suggesting an acute hypersensitivity reaction to the drug. The acute renal failure in all cases was non-oliguric and was completely reversed after discontinuation of ciprofloxacin. In two of the three reported cases there was an increased creatinine to BUN ratio, but increased production of creatinine (i.e., rhabdomyolysis) was unlikely with a normal serum creatinine phosphokinase (CPK). In addition, we performed in vitro studies which eliminated the possibility of methodological artifact. The nephrotoxicity of the quinolones has been linked to the development of crystalluria in experimental animals. However, in humans, crystalluria is unlikely and renal damage has not been noted. There have been only two previous case reports of acute renal failure due to oral ciprofloxacin therapy. In one, biopsy showed acute interstitial nephritis. We conclude that oral ciprofloxacin therapy may lead to acute renal failure secondary to tubulointerstitial nephritis characterized by an increased creatinine to BUN ratio. Patients placed on ciprofloxacin therapy need to be followed closely.

Methimazole-Induced ANCA Vasculitis: A Case Report.

Rapidly progressive glomerulonephritis (RPGN) is a syndrome which presents rapid loss of renal function. Vasculitis represents one of the major causes, often related to anti-neutrophil cytoplasmic antibodies (ANCA). Herein, we report a case of methimazole-induced ANCA-associated vasculitis. A 35-year-old woman complained of weight loss and fatigue for 2 weeks and attended the emergency room with alveolar hemorrhage. She had been diagnosed with Graves' disease and had been taking methimazole in the past 6 months. Her physical examination showed pulmonary wheezing, hypertension and signs of respiratory failure. Laboratory tests revealed urea 72 mg/dL, creatinine 2.65 mg/dL (eGFR CKD-EPI: 20 mL/min/1.73 m<sup2</sup), urine analysis with >100 red blood cells per high-power field, 24 h-proteinuria: 1.3 g, hemoglobin 6.6 g/dL, white-cell count 7700/mm<sup3</sup, platelets 238,000/mm<sup3</sup, complement within the normal range, negative viral serological tests and ANCA positive 1:80 myeloperoxidase pattern. Chest tomography showed bilateral and diffuse ground-glass opacities, and bronchial washing confirming alveolar hemorrhage. A renal biopsy using light microscopy identified 27 glomeruli (11 with cellular crescentic lesions), focal disruption in glomerular basement membrane and fibrinoid necrosis areas, tubulitis and mild interstitial fibrosis. Immunofluorescence microscopy showed IgG +2/+3, C3 +3/+3 and Fibrinogen +3/+3 in fibrinoid necrosis sites. She was subsequently diagnosed with crescentic pauci-immune glomerulonephritis, mixed class, in the setting of a methimazole-induced ANCA vasculitis. The patient was treated with methimazole withdrawal and immunosuppressed with steroids and cyclophosphamide. Four years after the initial diagnosis, she is currently being treated with azathioprine, and her exams show creatinine 1.30 mg/dL (eGFR CKD-EPI: 52 mL/min/1.73 m<sup2</sup) and negative p-ANCA.

Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial.

Acute pyelonephritis is a common infection in adult women, but there is a paucity of controlled trials of its treatment and the optimum duration of antibiotic treatment has not been properly defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with community-acquired acute pyelonephritis. In a prospective, non-inferiority trial undertaken at 21 centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A computer-generated randomisation list in block sizes of two was used for treatment allocation in a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily according to the randomisation code. Patients, carers, site investigators, and trial coordinating centre staff were masked to group assignment. The primary endpoint was the clinical and bacteriological outcome 10-14 days after completion of treatment with active drug. Analysis was by per protocol. This trial is registered with EudraCT, number 2005-004992-39, and ClinicalTrials.gov, number ISRCTN73338924. 126 of 248 patients were randomly assigned to 7 days and 122 to 14 days of ciprofloxacin. 73 and 83 patients, respectively, were analysed. Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days (difference -0·9%; 90% CI -6·5 to 4·8; p=0·004; non-inferiority test). Cumulative efficacy at long-term follow-up was 93% in each group (68 of 73 vs 78 of 84; -0·3%; -7·4 to 7·2; p=0·015). Both regimens were well tolerated. Two patients discontinued ciprofloxacin because of myalgia with 7 days of treatment and itching exanthema with 14 days. Four (5%) of 86 patients assigned to 7 days of treatment who complied with study criteria and six (6%) of 93 assigned to 14 days reported an adverse event after the first week of treatment that was possibly or probably related to the study drug. In those assigned to 7 days, no patient had mucosal candida infection after the first week versus five treated for 14 days (p=0·036). Our results show that acute pyelonephritis in women, including older women and those with a more severe infection, can be treated successfully and safely with oral ciprofloxacin for 7 days. Short courses of antibiotics should be favoured in an era of increasing resistance. Swedish Strategic Programme against Antibiotic Resistance (Strama).

Contrast-induced nephropathy

Decreased kidney function European guidelines classify a pre-existing decreased kidney function to be a risk factor of contrast-induced nephropathy in the following cases: Estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2 of body surface area before intra-arterial administration with first-pass renal exposure (not passing lungs or peripheral circulation before kidneys), or in the intensive care unit eGFR < 30 ml/min/1.73 m2 before intravenous administration or intra-arterial administration with second-pass renal exposure Known or suspected acute kidney injury To calculate estimated GFR from creatinine, European guidelines use the CKD-EPI formula in adults ≥ 18 years, and the revised Schwartz formula in children. Swedish guidelines recommends no specific formula in children because of lack of evidence, but on the other hand recommends GFR based on cystatin C rather than creatinine in those with abnormal muscle mass or liver failure or cirrhosis.

Chronic granulomatous interstitial nephritis: unusual complication of acute pyelonephritis.

We describe an unusual complication of acute pyelonephritis in a 45-year-old diabetic female. She was admitted to our hospital due to fever and flank pain which had developed 10 days earlier. Urinalysis showed many WBC and urine culture revealed Escherichia coli. After adequate antibiotic treatment, clinical symptoms abated but renal failure and leukocyturia persisted. Abdominal CT showed bilateral focal bacterial nephritis and renal biopsy disclosed chronic granulomatous interstitial nephritis. On the 80th hospital day she was discharged with a serum creatinine of 299 mumol/l. In the outpatient clinic, renal dysfunction and leukocyturia persisted up to 1 year. In conclusion, this case raises the possibility of a chronic interstitial process of acute pyelonephritis.

[Acute tubulointerstitial nephritis in children].

Acute tubulointerstitial nephritis (ATIN) is a rare renal disorder in children. Patients usually present non-specific symptoms and signs so that the diagnosis of ATIN is often delayed. The disease may be infection- or drug-induced or it may occur without a known cause. Early recognition and appropriated therapy usually lead to an excellent prognosis. The aim of the study was to describe clinical and laboratory findings and the course of ATIN in 21 patients, that are typical enough to enable early recognition of the disease as it is potentially reversible. Between 1986 and 1997 we observed 21 patients, aged 7-16 years (mean, 12.8), with acute tubulointerstitial nephritis, including eight with tubulointerstitial nephritis and uveitis (TINU syndrome). Laboratory studies included urinalysis, complete blood count, erytrocyte sedimentation rate (ESR), plasma creatinine, glomerular filtration rate (GFR), electrolytes, proteins, IgG, C3, C4 antinuclear-antibodies (ANA), antistreptolysin-O and antibodies to hantaviruses. Renal ultrasound was done in all patients. Renal biopsy was performed in 5 children. All children had previously been healthy. The symptoms of ATIN developed within a few days (Table 1). The most common initial symptoms were fatigue, fever, gastrointestinal disturbances, anorexia and weight loss. Less common complaints included headache, arthralgias and maculopapular rash. On addmition no patient had hypertension, oedema or evidence of acute infection. ESR, plasma urea and creatinine concentrations were increased in all, plasma proteins and IgG levels in the majority of patients. ANA were negative in 15 pts in whom this analysis was performed; C3 and C4 levels were normal. In two children recent strepococcal and in the other 6 hantavirus infection was serologicaly proved. All patients had non-oliguric acute renal failure (ARF): GFR was 21.7 +/- 8 9 in 14 pts and 67 +/- 9.7 in 7 pts. Low urine specific gravity (1003-1014), mild proteinuria (0.3-0.4 g/24 h), leukocyturia and/or haematuria were found in all patients; glycosuria, aminoaciduria and decreased tubular reaposrption of phosphate (TRP) were found in 12/21, 9/21 and 9/14 patients, respectively. Urine cultures were negative in all children. Renal US demonstrated enlarged hyperechoic kidneys in 11 pts, in remaining 10 pts no abnormalities were found. Renal biopsy, performed in 5 children, confirmed the diagnosis of ATIN. Eight patients subsequently developed anterior uveitis as part of TINU syndrome. Treatment included supportive therapy in all and six patients received prednisolone for 4-8 weeks (40-60 mg/m2/24 h for 10-14 days with subsequent reduction of dose over several weeks). Anterior uveitis was successfully treated with topical steroids. Renal function completely recovered in all patients: GFR (109 +/- 22.6 ml/min) within a mean interval of 47 +/- 33 days, concentration ability within 2-12 (mean 4.5) months. Common clinical features of ATIN are non-oliguric acute renal failure of various degrees, signs of tubular dysfunction, proteinuria, haematuria, leukocyturia and absence of hypertension. All our patients had normal blood pressure, non-oliguric renal failure, proteinuria, hypostenuria and abnormal urinary sediment; about half of them had glycosuria and/or other signs of proximal tubular dysfunction. The most important causes of ATIN in children reported in literature are systemic infections and drugs. However, the cause of ATIN in our patients was assessed as being related to infection only in 8 patients and to diclofenac in one. No infection, drug, toxin or other cause could be identified in 4, as well as in 8 pts with TINU syndrome. The prognosis of ATIN in children is considered to be favourable, but some patients may develop chronic renal failure. Renal function completely recovered in all our patients; that is consistent with outcome data from the most reports. Acute tubulointerstitial nephritis is an important cause of ARF in children, its aetiology may be different and it carries an excellent prognosis. ATIN should be suspected in a child who presents typical, although non-specific symptoms and signs, associated with lukocyturia and/or microhaematuria, signs of tubular dysfunction and unexplained renal failure. The diagnosis can be verified at renal biopsy. Early recognition of the disease is important to remove possible aetiologic agents and to treat them before chronic lesions are present to avoid long-term renal damage.

[Acute interstitial nephritis in childhood].

Acute tubulointerstitial nephritis (TIN) was diagnosed during a 10-year period in 6 previously healthy children (4 boys) with a mean age of 10 years (range 2.5-14 years). All presented with a non-specific history. First laboratory findings were nearly identical, with a raised erythrocyte sedimentation rate and non-oliguric renal failure; the urine contained protein, glucose, and leucocytes, but no bacteria. A serologically proven infection (streptococcal infection 2x; mononucleosis 1x) or drug-related TIN (penicillin) was present in 4 children; in one, both conditions could have been responsible. One girl suffered from idiopathic TIN with uveitis. Rapid progression of renal failure occurred in 3 children, but the response to steroid therapy was satisfactory. No dialysis was necessary and all patients showed a complete recovery. We think that acute TIN occurs more frequently than suggested previously. Many episodes are probably mild or subclinical and the rate of spontaneous remission is high. The results of initial laboratory evaluation in conjunction with acute renal failure and predominantly proximal tubular dysfunction, are sufficiently typical to arouse suspicion of acute TIN at an early stage, although they do not permit any conclusion as to the aetiology.

[Tubulo-interstitial nephritis and uveitis syndrome--TINU syndrome].

Acute tubulo-interstitial nephritis and uveitis (TINU syndrome) in a 53-year-old woman is reported. This rare syndrome was described 27 years ago by Dobrin et al. Since then about 50 cases have been described. The syndrome can appear at any age but most patients are under 20 years; about 75% are females. Clinical characteristics include fatigue, general malaise, weight loss, fever, night sweats, anorexia, nausea and vomiting, pallor, nocturia, polyuria, arthralgia and skin rash. Ocular involvement usually includes anterior uveitis but is sometimes posterior; in most cases the uveitis is bilateral. The characteristic laboratory findings are anemia, rapid sedimentation rate, decreased glomerular filtration rate with increased serum creatinine and urea. Total protein is increased because of polyclonal gammopathy and elevated beta 2-microglobulin. Urinalysis characteristically reveals proteinuria and beta 2-microglobulinuria. The histopathologic features on renal biopsy are characteristic of tubulo-interstitial nephritis. Uveitis can precede, accompany or follow onset of the nephropathy. The pathogenesis and etiology of the syndrome are as yet unknown. Treatment consists of large doses of corticosteroids, but the necessity for treatment is unclear, since there is evidence of spontaneous improvement. Although the prognosis of the nephropathy is favorable and most cases are reversible, the uveitis tends to recur.

Clinical Manifestations and Outcomes of Fluoroquinolone-Related Acute Interstitial Nephritis.

To describe the clinical presentation, diagnosis, and outcomes of patients with biopsy-proven acute interstitial nephritis (AIN) related to fluoroquinolone (FQ) therapy. We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic's campus in Rochester, Minnesota, from January 1, 1993, through December 31, 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy-proven AIN that were attributed to FQ use. We identified 24 patients with FQ-related biopsy-proven AIN at our institution. The most commonly prescribed FQ was ciprofloxacin in 17 patients (71%), and the median antibiotic treatment duration was 7 days (interquartile range [IQR], 5-12 days). The median time from the initiation of FQ to the diagnosis of AIN was 8.5 days (IQR, 3.75-20.75 days). Common clinical manifestations included fever (12; 50%), skin rash (5; 21%), and flank pain (2; 8%), and 9 (38%) had peripheral eosinophilia. However, 4 (17%) of the patients were asymptomatic at the time of diagnosis and AIN was suspected on the basis of routine laboratory monitoring. Most patients (17; 71%) recovered after the discontinuation of antibiotic therapy, and renal function returned to baseline at a median of 20.5 days (IQR, 11.75-27.25 days). Six patients (25%) required temporary hemodialysis, and 14 patients (58%) received corticosteroid therapy. The onset of FQ-related AIN can be delayed, and a high index of suspicion is needed by physicians evaluating these patients. Overall outcomes are favorable, with recovery to baseline renal function within 3 weeks of discontinuing the offending drug.

Ciprofloxacin

Ciprofloxacin occupies an important role in treatment guidelines issued by major medical societies for the treatment of serious infections, especially those likely to be caused by Gram-negative bacteria, including Pseudomonas aeruginosa. For example, ciprofloxacin in combination with metronidazole is one of several first-line antibiotic regimens recommended by the Infectious Diseases Society of America for the treatment of community-acquired abdominal infections in adults. It also features prominently in treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary tract infection, acute or chronic prostatitis, certain types of endocarditis, certain skin infections, and prosthetic joint infections.

Acute renal failure due to ciprofloxacin.

Acute renal failure developed in three patients within a few days of starting ciprofloxacin hydrochloride therapy. An allergic interstitial nephritis was suggested by fever and eosinophiluria in one patient and by erythema multiforme in another. A kidney biopsy specimen confirmed this diagnosis in one patient. Renal function improved shortly after withdrawal of the drug in all three patients. Literature survey revealed an additional three patients with a similar complication. Allergic manifestations, such as fever or rash, were a feature in most reported cases. In view of this potential complication, renal function should be closely monitored in patients receiving ciprofloxacin therapy, especially if other potentially nephrotoxic drugs are prescribed concomitantly.

Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.

Targeted cancer therapies have revolutionized the field of oncology by selecting for specific molecular pathways, thus improving overall clinical prognosis. However, many of these targeted treatments have been reported to have adverse kidney effects, including acute kidney injury, interstitial nephritis, and glomerular disease. Furthermore, some of these targeted therapies have also been found to cause an asymptomatic rise in serum creatinine levels through inhibition of active tubular secretion. A 79-year-old woman was being followed for stage 4 A2 chronic kidney disease secondary to type 2 diabetes and longstanding hypertension. She was diagnosed with invasive mammary carcinoma and was initiated on letrozole, an aromatase inhibitor, and palbociclib, a selective cyclin-dependent kinase inhibitor, was subsequently added. Prior to the initiation of her treatments, her baseline estimated glomerular filtration rate (eGFR) fluctuated between 25 and 28 mL/min/1.73 m<sup2</sup over the previous year. After initiating palbociclib, her serum creatinine progressively increased, despite having well-controlled blood pressure and diabetes. In addition, there was no history of pre-renal events nor any sonographic evidence of obstruction. Within 7 months, her eGFR based on serum creatinine had decreased down to 12 mL/min/1.73 m<sup2</sup. Given that there were no clinical or other biochemical changes suggestive of worsening renal function, a serum cystatin C was measured using an immunoturbidimetric assay, which was 1.71 mg/L and correlated with an eGFR of 33 mL/min/1.73 m<sup2</sup based on the chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C equation (2012). This value was consistent with her previous baseline. Based on these findings, the significant decrease in eGFR measured by serum creatinine was attributed to the inhibitory effects of palbociclib on tubular creatinine secretion, rather than representing true kidney damage. Thus, a kidney biopsy was not performed in this context. Seven months later, a repeat serum cystatin C was repeated to assess for any worsening of the patient's kidney function and revealed an eGFR of 35 mL/min/1.73 m<sup2</sup based on the CKD-EPI cystatin C equation (2012), thus revealing stable kidney function and reinforcing the inhibitory effects of palbociclib on tubular creatinine secretion through its direct effects on kidney transporters. This case report and literature review acknowledges the importance of using alternative methods of assessing kidney function when patients are undergoing targeted cancer therapies known to affect tubular creatinine secretion, which include cyclin-dependent kinase 4/6 inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, tyrosine kinase inhibitors, and mesenchymal-epithelial transition inhibitors. The use of non-creatinine-based markers of glomerular filtration rate (GFR), such as cystatin C and nuclear renal scans, will allow for more accurate estimation of kidney function in the appropriate setting, thus avoiding invasive diagnostic tests and unnecessary adjustments of treatment plans. However, certain targeted cancer therapies have also been proven to cause true kidney injury; therefore, physicians must still maintain a high degree of suspicion and consider invasive investigations and/or cessation or reduction of treatments when alternative measurements of kidney function do not suggest an underestimation of GFR via serum creatinine.

Late sequelae of adult-onset acute bacterial nephritis.

The late manifestations of adult-onset acute bacterial nephritis were studied in four patients from 4 months to 5.6 years following initial infection. An unusual combination of generalized (global) wasting of the kidney and focal calyceal clubbing developed within a few weeks of the acute infection. The pattern of calyceal deformity strongly suggests papillary necrosis; it may develop during the acute phase, but go unrecognized during excretory urography at that time because of impaired contrast material excretion. The combination of a small, smooth kidney and papillary necrosis previously has been associated only with the more severe forms of analgesic nephropathy. Observations in these patients indicate that the same urographic findings may also occur as a result of a single earlier episode of acute bacterial infection of the kidney.

Drug-induced acute tubulointerstitial nephritis: a case with elevated urinary cadmium.

Acute tubulointerstitial nephritis (ATIN) has many different causes, but is most frequently caused by drugs. We report a 13-year-old vegetarian girl with drug-induced ATIN, confirmed by renal biopsy, and simultaneous occurrence of elevated urinary cadmium. Four weeks prior to admission she had been treated with antibiotics and acetaminophen for respiratory infection, and remaining febrile, was treated with different "home-made" herbal mixtures. She presented with acute non-oliguric renal failure, tubular dysfunction, and sterile pyuria, but without skin rash or edema. Laboratory data showed a raised erythrocyte sedimentation rate, normal white blood count with eosinophilia, and a serum creatinine of 245 micromol/l. Urinalysis was remarkable for glycosuria, tubular proteinuria, and elevated beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase excretion. Immunoserological tests characteristic of acute glomerulonephritis and systemic diseases were negative. She was treated with steroids and her renal function improved. Follow-up analyses disclosed normal urinary cadmium and enzyme excretion within 6 months. Heavy metal analysis of herbal preparations that she had taken confirmed the presence of cadmium, but within approved concentrations. In conclusion, elevated urinary cadmium in the case of drug-induced ATIN may be assumed to be an accidental finding. However, consumption of different herbs containing cadmium and cadmium-induced nephro-toxicity could be the reason for such serious renal damage.

[Fluoroquinolone induced acute renal failure. General review about a case report with crystalluria due to ciprofloxacin].

A 58 year-old woman developed an acute renal failure very quickly after ingestion of two 500 mg tablets of ciprofloxacin, without any other identifiable risk factor. Renal biopsy was performed. No sign of acute interstitial nephritis was observed but tubular lesions were found, accompanied by deposits of a brown-yellowish substance identified by infrared microscopy as a ciprofloxacin salt. The outcome was favourable. This observation gives the opportunity to remind the different forms of quinolone-induced renal injury and to discuss the possible ways for preventing renal side-effects related to the quinolone use.

[A case of microscopic polyangitis with sepsis due to pyelonephritis].

A 69-year-old woman, who had been diagnosed with interstitial pneumonia at 66 years of age, was admitted to our hospital because of high fever, purpura occurring on her arms and legs, and renal dysfunction. At the time of admission, her renal function had severely deteriorated (sCr 8.2 mg/dl, 24 h Ccr 6 ml/min), she had a severe high fever (BT 39.5 degrees C), back pain, a white blood cell count of 19,540/,microl, and a CRP level of 26.7 mg/dl. Blood and urine cultures yielded identical strains of E. coli. We diagnosed sepsis caused by pyelonephritis, and started intravenous meropenem trihydrate(MEPM) at 0.5 g/day. Her renal dysfunction was severe, so we started hemodialysis therapy. Immunological examination revealed the presence of ANCA-associated glomerulonephritis. Renal biopsy before steroid therapy confirmed the diagnosis of pauci-immune-type crescentic glomerulonephritis. Based on purpura and interstitial pneumonia, along with rapidly MPO-ANCA-positive progressive glomerulonephritis (RPGN) with acute renal failure, we diagnosed microscopic polyangitis (MPA). To treat sepsis and severe pyelonephritis, we started intravenous immunoglobulin 5 g (100 mg/kg)/day for 5 days before starting immunosuppressive steroid therapy (m-PSL 1 g/day, PSL 20 mg/day) for 3 days. These treatments improved her general condition and immediately improved her renal function. It is important to prevent infection during treatment using conventional immunosuppressive therapy. These findings suggest immunoglobulin therapy to be a safe immuno-suppressive treatment that is efficacious against ANCA-associated glomerulonephritis.

[Long-term monitoring of female acute uncomplicated cystitis cases after lomefloxacin single-dose therapy].

Female acute uncomplicated cystitis responds relatively well to antimicrobial chemotherapy, but this is also a disease which shows a high frequency of recurrence. However, there have been no published reports regarding long-term monitoring of the course of this disease after therapy has been administered. Accordingly, using primarily a questionnaire, the authors carried out long-term monitoring (for a mean of 242 days) of the natural course of cases of female acute uncomplicated cystitis after single-dose therapy with lomefloxacin (LFLX), a new quinolone antimicrobial agent. The subjects of this study were female patients diagnosed as having acute uncomplicated cystitis with pain upon urination, pyuria (> or = 10 WBCs/hpf) and bacteriuria (> or = 10(4) cfu/ml). LFLX was orally administered as a single dose of 100 mg or 300 mg, and the therapeutic efficacy was evaluated on the 3rd and 7th days thereafter. In principle, the evaluation of cure was performed on the 7th day after LFLX administration, and monitoring was conducted to detect early recurrence during the next 7 days (i.e., through the 14th day after treatment). Then the subjects were monitored for late recurrence during a mean follow-up period of 242 days by means of a questionnaire. Confirmation of recurrence was carried out to the greatest extent possible. It was possible to carry out long-term monitoring of the natural course of 101 cases of female acute uncomplicated cystitis in which the clinical efficacy on the 3rd day after LFLX treatment had been evaluated as good or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Kidney failure

Acute kidney failure Acute kidney injury (AKI), previously called acute renal failure (ARF), is a rapidly progressive loss of renal function, generally characterized by oliguria (decreased urine production, quantified as less than 400 mL per day in adults, less than 0.5 mL/kg/h in children or less than 1 mL/kg/h in infants); and fluid and electrolyte imbalance. AKI can result from a variety of causes, generally classified as prerenal, intrinsic, and postrenal. Many people diagnosed with paraquat intoxication experience AKI, sometimes requiring hemodialysis. The underlying cause must be identified and treated to arrest the progress, and dialysis may be necessary to bridge the time gap required for treating these fundamental causes. Chronic kidney failure Chronic kidney disease (CKD) can also develop slowly and, initially, show few symptoms. CKD can be the long term consequence of irreversible acute disease or part of a disease progression.

Management of acute renal failure in the elderly. Treatment options.

Renal changes that occur with aging mainly consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increase the risk of volume depletion and the prerenal type of acute renal failure (ARF) in elderly people. Bladder outlet obstruction caused by benign prostatic hypertrophy is a common cause of ARF in elderly men. Another frequent cause of ARF in the elderly is drug-induced nephropathy. Nonsteroidal anti-inflammatory drugs (NSAIDs) and antibiotics are most often implicated in the development of ARF in the elderly. However, considering the high usage of these drugs, the incidence of drug-induced nephropathy is relatively small. NSAIDs are more likely to cause ARF in patients with congestive heart failure, chronic renal disease (including diabetic nephropathy) or chronic liver disease than in otherwise healthy individuals. NSAID-induced ARF is often of the prerenal type, but may be caused by acute interstitial nephritis (AIN). The presence of heavy proteinuria or nephrotic syndrome differentiates NSAID-induced AIN from AIN caused by other drugs. Antibiotics, especially semisynthetic penicillins, more commonly give rise to AIN associated with peripheral blood eosinophilia and eosinophiluria than NSAIDs. Ciprofloxacin is increasingly reported to cause AIN. Fever commonly accompanies AIN, especially when induced by antibiotics. Aminoglycosides produce ARF by inducing acute tubular necrosis (ATN), which results from the excessive accumulation of myeloid bodies in the tubules. In all cases of ARF it is essential to obtain a good history, to perform a through physical examination, with particular attention to skin turgor, and to measure blood pressure, pulse rate (supine and upright), urinary electrolyte and creatinine levels. Fractional excretion of sodium and the urine:plasma creatinine ratio are reliable indices that distinguish prerenal ARF from ATN. A prompt response to fluid challenge, with an increase in urine output and urinary sodium excretion, and a rapid decrease in blood urea nitrogen, constitutes strong evidence for prerenal ARF. However, these indices are unreliable when prerenal ARF has progressed to ATN or when ARF has an obstructive pattern to begin with. In all cases of ARF, especially in elderly men, urinary tract obstruction should be suspected unless the history is otherwise clear cut. Ultrasound of the kidneys and bladder is a simple, non-invasive and meaningful test that can be used to rule out obstructive causes of ARF. If obstruction is the cause of ARF, ultrasound will be positive; in contrast, urinary obstruction is very unlikely if ultrasound findings are normal in a patient who has been oliguric or anuric for 48 hours or more. Similarly, acute glomerulonephritis, including rapidly progressive glomerulonephritis, should be suspected when ARF is associated with heavy proteinuria. In such instances, percutaneous renal biopsy is essential to document the diagnosis. It is of utmost importance to establish whether ARF is of prerenal or postrenal type, both of which are potentially fully reversible. In contrast, patients with ATN or rapidly progressive glomerulonephritis may not recover, or may only partially recover, their renal function. Haemodialysis and nutritional support are common measures for patients with severe ATN and a highly catabolic state. Corticosteroids and immunosuppressive therapy should be instituted for rapidly progressive glomerulonephritis, in addition to haemodialysis. haemodiafiltration instead of haemodialysis is recommended for patients who are haemodynamically unstable [i.e., with a persistently low blood pressure (systolic < or = 100 mm Hg)]. Haemodiafiltration has been shown to improve acid-base balance and uraemia better than standard haemodialysis. However, despite dialysis, mortality in patients with ARF associated with ischaemic ATN remains high.

Drug-induced tubulointerstitial nephritis and uveitis syndrome with posterior uveitis resembling acute posterior multifocal placoid pigment epitheliopathy.

To report the occurrence of acute posterior multifocal placoid pigment epitheliopathy (APMPPE)-like posterior uveitis as part of the ocular manifestation of tubulointerstitial nephritis and uveitis (TINU) syndrome. A 54-year-old previously healthy woman received oral ibuprofen and dipirone because of high fever and malaise. Three days after being started on this treatment, she developed bilateral posterior uveitis resembling APMPPE accompanied by anterior segment inflammation in the context of acute renal nephritis and maculopapular skin rash probably related to drug exposure. The patient was hospitalized because of acute renal failure and received support therapy and topical steroids in both eyes. A renal biopsy was not performed (based on good clinical response), but she fulfilled the clinical criteria of acute interstitial nephritis and TINU. Although her renal and ocular functions improved in the first week, she needed to be readmitted days later because of fever and generalized edema and received steroid pulse therapy. Fluorescein angiography was consistent with an APMPPE-like pattern and optical coherence tomography showed neither macular edema nor subretinal fluid. The ocular picture improved during the following weeks with fundus changes resembling those of APMPPE. Although anterior uveitis is considered the typical ocular component of TINU syndrome, posterior uveitis resembling APMPPE may also be its ocular manifestation.

[Acute renal failure as a complication of cholera].

We present a 72-year-old man who had episodes of severe, acute renal failure during severe attacks of diarrhea caused by Vibrio cholerae. Patterns of acute tubular necrosis and tubulointerstitial nephritis developed following hypotension and decrease in renal blood flow, causing secondary renal ischemia. There was severe dehydration with profound hypovolemia and infection. The clinical picture included fever, weakness, arthralgia, pedal edema, mild bilateral pleural effusions, anemia, leukocytosis, azotemia with a maximum of 330 mg/dl of urea, creatine to a maximum of 9.8 mg/dl, hypoproteinemia, severe metabolic acidosis, marked increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), microscopic hematuria, sterile leukocyturia, normoglycemic glucosuria and phosphaturia with diminished tubular reabsorption of phosphorus. A short oliguric phase was followed by a polyuric phase lasting about 10 days, and glomerular and tubular function became normal after about 3 weeks. Treatment was by intensive infusions of fluids, electrolytes, sodium bicarbonate, salt-free albumin and antibiotics. To the best of our knowledge, this renal complication of cholera has not yet been described in Israel.

Ciprofloxacin

Ciprofloxacin was patented in 1980 and introduced in 1987. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies ciprofloxacin as critically important for human medicine. It is available as a generic medication. In 2019, it was the 113th most commonly prescribed medication in the United States, with more than 5million prescriptions. Medical uses Ciprofloxacin is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid. Ciprofloxacin only treats bacterial infections; it does not treat viral infections such as the common cold. For certain uses including acute sinusitis, lower respiratory tract infections and uncomplicated gonorrhea, ciprofloxacin is not considered a first-line agent.

A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis.

A clinical study was conducted to compare the efficacy and safety of levofloxacin 750 mg once daily for 5 days to ciprofloxacin twice daily for 10 days for the treatment of complicated urinary tract infections (cUTI) or acute pyelonephritis (AP). A multicenter, double-blind, randomized, noninferiority study enrolled subjects with AP or cUTI. Subjects received either levofloxacin 750 mg intravenously or orally once daily for 5 days or ciprofloxacin 400 mg intravenously and/or ciprofloxacin 500 mg orally twice daily for 10 days and were evaluated at end of therapy, posttherapy, and poststudy for microbiologic eradication and clinical outcome. A total of 1109 subjects were enrolled; 619 with confirmed diagnosis of AP or cUTI and a study entry uropathogen with a colony count 10(5) CFU/mL or greater and were included in the modified intent-to-treat population. Five hundred six subjects met all criteria for inclusion and were included in the microbiologically evaluable population. At end of therapy, eradication rates in the modified intent-to-treat population were 79.8% for levofloxacin and 77.5% for ciprofloxacin-treated subjects (95% CI, -8.8% to 4.1%). In the microbiologically evaluable population, eradication rates were 88.3% for levofloxacin and 86.7% for ciprofloxacin-treated subjects (95% CI, -7.4% to 4.2%). Outcomes were comparable for the 2 treatments at posttherapy and poststudy. This study demonstrates that both drug regimens are safe and effective and that a 5-day course of therapy with levofloxacin, administered at a dose of 750 mg once daily, is noninferior to a 10-day course of therapy with ciprofloxacin for the treatment of AP and cUTI.


You have probably looked at answer 5, hereditary spherocytosis, associated with biliary lithiasis at an early age. Exactly, that is the correct one. In the statement they have not stopped giving clues: conjunctival jaundice, splenomegaly and family history of biliary lithiasis at an early age. He has reached 30 years of age without suffering a hemolytic crisis, without suffering any symptoms. There was no mention of microcytosis or macrocytosis to suggest thalassemia minor or B12 and/or folic acid deficiency. Nor of hemolytic crisis associated with the consumption of drugs, infections or ingestion of beans or peas. They have not given any clues to stop to think about other possibilities.

You have probably looked at answer 5, hereditary spherocytosis, associated with biliary lithiasis at an early age. [HIDDEN]. In the statement they have not stopped giving clues: conjunctival jaundice, splenomegaly and family history of biliary lithiasis at an early age. He has reached 30 years of age without suffering a hemolytic crisis, without suffering any symptoms. There was no mention of microcytosis or macrocytosis to suggest thalassemia minor or B12 and/or folic acid deficiency. Nor of hemolytic crisis associated with the consumption of drugs, infections or ingestion of beans or peas. They have not given any clues to stop to think about other possibilities.

A 30-year-old woman, asymptomatic, is found to be anemic on routine examination. Physical examination reveals conjunctival jaundice and splenomegaly. The patient refers to a family history of biliary lithiasis at an early age. All this suggests the most probable diagnosis of:

Glucose 6-phosphate dehydrogenase deficiency.

Vitamin Bl2 and/or folic acid deficiency.

Misdiagnosis of two cases of hereditary spherocytosis in a family and review of published reports.

Hereditary spherocytosis is usually diagnosed based on a combination of clinical and family histories, physical examination, and laboratory data. Milder or atypical cases can be difficult to diagnose. We report one case each of mild and moderate hereditary spherocytosis whose diagnoses were made by the First Affiliated Hospital, Guangxi Medical University in China. In case 1, laboratory test results were as follows: hemoglobin 81.40 g/l, mean corpuscular hemoglobin concentration 339.00 g/l, mean corpuscular volume 82.88 fl, reticulocyte count 19%, mean sphered corpuscular volume 71.66 fl, total bilirubin 57.60 μmol/l, and blood smears showed increased spherocytosis. In case 2, laboratory test results were as follows: hemoglobin 133.10 g/l, mean corpuscular hemoglobin concentration 358.60 g/l, mean corpuscular volume 96.75 fl, reticulocyte count 17%, mean sphered corpuscular volume 77.78 fl, total bilirubin 62.50 μmol/l, and blood smears showed increased spherocytosis. Mild and moderate hereditary spherocytosis can be easily misdiagnosed. Assessment of total, direct, and indirect serum bilirubin, erythrocyte morphology and red cell characteristics (particularly mean corpuscular volume and mean sphered corpuscular volume) clearly distinguishes hereditary spherocytosis from autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, thalassemia, and autoimmune hepatitis.

Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias.

Congenital hemolytic anemias (CHAs) comprise defects of the erythrocyte membrane proteins and of red blood cell enzymes metabolism, along with alterations of erythropoiesis. These rare and heterogeneous conditions may generate several difficulties from the diagnostic point of view. Membrane defects include hereditary spherocytosis and elliptocytosis, and the group of hereditary stomatocytosis; glucose-6-phosphate dehydrogenase and pyruvate kinase, are the most common enzyme deficiencies. Among ultra-rare forms, it is worth reminding other enzyme defects (glucosephosphate isomerase, phosphofructokinase, adenylate kinase, triosephosphate isomerase, phosphoglycerate kinase, hexokinase, and pyrimidine 5'-nucleotidase), and congenital dyserythropoietic anemias. Family history, clinical findings (anemia, hemolysis, splenomegaly, gallstones, and iron overload), red cells morphology, and biochemical tests are well recognized diagnostic tools. Molecular findings are increasingly used, particularly in recessive and de novo cases, and may be fundamental in unraveling the diagnosis. Notably, several confounders may further challenge the diagnostic workup, including concomitant blood loss, nutrients deficiency, alterations of hemolytic markers due to other causes (alloimmunization, infectious agents, rare metabolic disorders), coexistence of other hemolytic disorders (autoimmune hemolytic anemia, paroxysmal nocturnal hemoglobinuria, etc.). Additional factors to be considered are the possible association with bone marrow, renal or hepatic diseases, other causes of iron overload (hereditary hemochromatosis, hemoglobinopathies, metabolic diseases), and the presence of extra-hematological signs/symptoms. In this review we provide some instructive clinical vignettes that highlight the difficulties and confounders encountered in the diagnosis and clinical management of CHAs.

InternalMed_Harrison

Hemolytic disorders that cause excessive heme production may be either inherited or acquired. Inherited disorders include spherocytosis, sickle cell anemia, thalassemia, and deficiency of red cell enzymes such as pyruvate kinase and glucose-6-phosphate dehydrogenase. In these conditions, the serum bilirubin level rarely exceeds 86 μmol/L (5 mg/dL). Higher levels may occur when there is coexistent renal or hepatocellular dysfunction or in acute hemolysis, such as a sickle cell crisis. In evaluating jaundice in patients with chronic hemolysis, it is important to remember the high incidence of pigmented (calcium bilirubinate) gallstones found in these CAuSES of iSoLATED HyPERBiLiRuBinEMiA PART 2 Cardinal Manifestations and Presentation of Diseases I. Indirect hyperbilirubinemia A. Hemolytic disorders 1. Inherited a. Spherocytosis, elliptocytosis, glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies b. 2. Acquired a. b. c. d. e. B. 1.

Homozygosity for dominant form of hereditary spherocytosis.

A 6-month-old male infant with hereditary spherocytosis (HS) who was the first child of a cousin marriage is presented. The patient had splenomegaly and severe anaemia. Examination of the peripheral blood smear revealed spherocytes and the osmotic fragility of red blood cells was greatly increased. Physical examination of the parents revealed that both parents had mild anaemia, jaundice and splenomegaly. Their peripheral blood smears showed spherocytes and a few acanthocytes. Osmotic fragility of red blood cells of both parents were increased. Red cell membrane electrophoresis indicated a deficiency of ankyrin in the propositus; mild deficiency was also detected in both parents. Electrophoretic patterns of red cell membrane proteins suggested that the child was homozygous for the dominant form of HS associated with ankyrin deficiency, while both parents had the simple dominant form of the disease. Red blood cell transfusions were given to the patient starting at the age of 1 month until splenectomy was performed at the age of 1 year that resulted in complete haematological response. This observation indicates that homozygosity for dominant type of HS associated with ankyrin deficiency is life compatible and splenectomy may cure the anaemia.

Glucose 6 phosphate dehydrogenase deficiency: A single-center experience.

This study aims to evaluate the demographic information, clinical and laboratory findings of patients with glucose 6 phosphate dehydrogenase deficiency. We collected data by reviewing files and electronic records of 65 patients with glucose 6 phosphate dehydrogenase deficiency under the age of 18 years who were followed up in our clinic between 2007 and 2019. Demographic, clinical, and laboratory features, family history, complications of the disease, and history of splenectomy and cholecystectomy were evaluated. Mean, standard deviation, and median values were used when descriptive analyses were presented. The age of diagnosis ranged between 1-192 months and the median age of diagnosis was two months. Fifty-nine patients (90.7%) were boys and six (9.2%) were girls. The mean value of glucose 6 phosphate dehydrogenase enzyme on admission was 1,9±1,4 U/g of hemoglobin (Hb). Family history was pesent in 40% of patients in whom information was avaliable. The most common presentation was prolonged jaundice and the most common physical finding was jaundice. Splenomegaly was detected in none of the patients. Cholelithiasis was present in one of 21 patients who were evaluated with ultrasonography. None of the patients required splenectomy, cholecystectomy, and regular erythrocyte transfusion during follow-up. As G6PD variants with chronic hemolysis are not usually seen in Turkey, patients who required splenectomy, cholecystectomy, and regular erythrocyte transfusion were not detected. Although glucose 6 phosphate dehydrogenase deficiency is more common in males, it can also be seen in girls. In Turkey, glucose 6 phosphate dehydrogenase deficiency should be considered in patients presenting with prolonged jaundice.

Pyruvate kinase deficiency in an alpha-thalassemia family: first case report in Thailand.

In Thailand, the most common cause of chronic hemolytic anemia is thalassemia hemoglobinopathy. We report here a 10-year-old girl with pyruvate kinase (PK) deficiency who was initially diagnosed to have Hb H disease, like her sister. The patient had a history of neonatal jaundice which required blood exchange transfusion twice and phototherapy. She became anemic and regular blood transfusion was required since the age of 2 1/2 months. She was very anemic compared to her sister and was transfusion dependent. Besides, she never had red cell inclusion bodies, thus re-evaluation was performed. The diagnosis of red cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved after cessation of blood transfusion for 3 months. The family study also confirmed the diagnosis. The patient is now on high transfusion and iron chelation. She is doing well with mild splenomegaly.

[Megaloblastic anemia due to folate deficiency associated with hereditary spherocytosis].

A 19 years old male admitted to our hospital with fever, abdominal pain in May 1991. Physical examination revealed anemia, jaundice and marked splenomegaly. Severe pancytopenia with macrocytic hyperchronic anemia was noted along with elevated LDH and reduced serum folate. Blood smear showed nucleated RBCs, but only few microspherocytes. Bone marrow showed erythroid hyperplasia with remarkable megaloblastic changes. Megaloblasts were negative for PAS stain. Chromosome analysis revealed normal karyotype. Erythroleukemia was suspected initially, but his general condition as well as hematological data improved following 10 units of RBC transfusion. Following brief folic acid supplements, numerous microspherocytes became evident, typical osmotic fragility test revealed a pattern for hereditary spherocytosis. These observations led us to the diagnosis of hereditary spherocytosis complicated by megaloblastic anemia due to folate deficiency. As he developed folate deficiency again 10 months later, splenectomy were performed. The anemia improved after splenectomy.

Disease-modifying influences of coexistent G6PD-deficiency, Gilbert syndrome and deletional alpha thalassemia in hereditary spherocytosis: A report of three cases.

Hereditary spherocytosis (HS) is a common inherited hemolytic anemia characterized by heterogeneous clinical presentations with variable degrees of anemia, jaundice, splenomegaly and gallstones. Although the underlying genetic defects in red cell membrane proteins may explain many phenotypic variations, a proportion of variability may be due to other co-inherited factors like enzymopathies, thalassemias and Gilbert syndrome. Associations of HS with glucose-6-phosphate dehydrogenase (G6PD) deficiency and Gilbert syndrome in isolation have been reported previously. We describe 3 adult cases of HS with concomitant Gilbert syndrome and G6PD-Mediterranean mutations (2 hemizygous males, aged 15 and 35y and 1 heterozygous 25-y female). Two patients required multiple transfusions that required splenectomy for management. One patient (15y male) also carried the single gene alpha 4.2 deletion and was less symptomatic. These cases illustrate the importance of clinico-pathological correlation and judicious extended testing for various contributing factors that may modify the clinical course of HS patients. G6PD deficiency is also a common enzymopathy in India and can contribute to the phenotypic heterogeneity. Its recognition is important for advising avoidance of oxidizing drug exposure.

Hereditary spherocytosis in a 27-year-old woman: case report.

Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to a fulminant hemolytic anemia. Although a positive family history of spherocytosis increases the risk for this disorder, it may be sporadic in some cases. In severe cases the disorder may be detected in early childhood, but in mild cases it may go unnoticed until later in adult life. A 27-year-old Nigerian woman presented with mild anemia, jaundice, splenomegaly and a history of multiple blood transfusion. Blood film showed about 70% spherocytes, reticulocytosis of 6.5%, increased osmotic fragility test and a negative direct antiglobulin test. She was managed conservatively on nutritional supplements and a significant regression of symptoms after 6 months was achieved.

Hereditary spherocytosis: experience of 145 cases.

145 patients were diagnosed to have hereditary spherocytosis (HS) over a period of 25 years. Jaundice (66.9%), fever (65.5%), weakness (44.8%), and abdominal pain (35.8%) were the commonest complaints. 94.5% had splenomegaly (JP-17 cm) and 71.7% had hepatomegaly (JP-6 cm). Spherocytes were detected in the peripheral smears of all patients at presentation on careful examination. 67 patients had been investigated elsewhere and spherocytes missed in 86.6%. Gall stones were seen in 20 of the 54 patients investigated. Family history suggestive of HS was available in only 16.6% of cases, whereas examination and investigations revealed HS in almost all families. Splenectomy was done in all symptomatic patients. In the 39 patients followed up for 1-9 years after splenectomy.

Jaundice

Prehepatic causes Prehepatic jaundice is most commonly caused by a pathological increased rate of red blood cell (erythrocyte) hemolysis. The increased breakdown of erythrocytes → increased unconjugated serum bilirubin → increased deposition of unconjugated bilirubin into mucosal tissue. These diseases may cause jaundice due to increased erythrocyte hemolysis: Sickle-cell anemia Spherocytosis Thalassemia Pyruvate kinase deficiency Glucose-6-phosphate dehydrogenase deficiency Microangiopathic hemolytic anemia Hemolytic-uremic syndrome Severe malaria (in endemic countries) Hepatic causes

Jaundice

Causes The most common cause of jaundice in infants is normal physiologic jaundice. Pathologic causes of neonatal jaundice include: Breastmilk jaundice Formula jaundice Hereditary spherocytosis Glucose-6-phosphate dehydrogenase deficiency Pyruvate kinase deficiency ABO/Rh blood type autoantibodies Alpha 1-antitrypsin deficiency Alagille syndrome (genetic defect resulting in hypoplastic intrahepatic bile ducts) Progressive familial intrahepatic cholestasis Pyknocytosis (due to vitamin deficiency) Cretinism (congenital hypothyroidism) Sepsis or other infectious causes Pathophysiology Transient neonatal jaundice is one of the most common conditions occurring in newborns (children under 28 days of age) with more than eighty percent affected during their first week of life. Jaundice in infants, like adults, is characterized by increased bilirubin levels (total serum bilirubin greater than 5 mg/dL).

Clinical Features and Outcome of Children With Hereditary Spherocytosis.

The aim of this study was to evaluate the demographics, clinical, and laboratory findings and treatment responses of patients with hereditary spherocytosis (HS). Data of children with HS were examined. Diagnosis was based on clinical history, physical examination, family history, presence of spherocytes on peripheral blood smear, and osmotic fragility test. A total of 101 patients were included. The median (range) age at diagnosis was 38.0 (1 to 188) months. Mild, moderate, and severe forms of HS were present in 29 (28.7%), 15 (14.9%), and 57 (56.4%) patients, respectively. Family history was available in 73 patients and 56 of these (76.7%) had a positive family history for HS. Forty-five (44.5%) patients needed regular transfusions and all of these had severe disease. Although most patients did not require transfusion postsplenectomy, 2 of 45 (4.4%) patients continued to require transfusion. Transfusion dependence was significantly (P<0.001) higher in patients with severe spherocytosis. In HS, splenomegaly, pallor, and jaundice are the most common clinical features. Splenectomy dramatically reduces hemolysis in most cases and virtually abolishes further requirement for transfusion.

Hereditary Spherocytosis  -- History and Physical

Most patients with hereditary spherocytosis have a positive family history. [8] This disease should be suspected in any child presenting with splenomegaly, anemia, and hyperbilirubinemia. Patients may also present with asymptomatic cholelithiasis of undetermined etiology, commonly with a positive family history. [7]

Hemolytic jaundice induced by pharmacological dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency: A case report.

Hemolysis induced by high dose ascorbic acid (AA) in patients with G6PD deficiency has been reported, but is rare. To our knowledge, this is the first reported case of a male with G6PD deficiency, coexpressed with cholecystolithiasis and cholecystitis, who developed extreme hemolysis and hyperbilirubinemia after receiving pharmacological doses ascorbic acid infusion. A 27-year-old man history with glucose-6-phosphate dehydrogenase deficiency was admitted to our hospital because of cholecystolithiasis and cholecystitis. He appeared with scleral jaundice and very deep colored urine after receiving pharmacological doses ascorbic acid infusion. Clinical findings when combined with his medical history and various laboratory results confirmed the diagnosis as hemolysis and hyperbilirubinemia induced by ascorbic acid. The patient was treated with steroids, hepatoprotective drugs, and folic acid in addition avoidance of agents with known hemolysis risk (such as vitamin C). As a result, the patient's symptoms from hemolytic jaundice improved, hemoglobin remained stable, and the patient was discharged 11 days later. Clinicians should bear in mind the possibility that vitamin C exposure may result in hemolysis in patients with G6PD deficiency, especially in those with known severe disease.

InternalMed_Harrison

A. Hemolytic disorders 1. Inherited a. Spherocytosis, elliptocytosis, glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies b. 2. Acquired a. b. c. d. e. B. 1. Cobalamin, folate, and severe iron deficiencies 2. C. Increased bilirubin production 1. 2. Resorption of hematoma D. Drugs 1. 2. 3. E. Inherited conditions 1. 2. II. A. B. patients, which increases the likelihood of choledocholithiasis as an alternative explanation for hyperbilirubinemia. lytic anemia (e.g., hemolytic-uremic syndrome), paroxysmal noc turnal hemoglobinuria, spur cell anemia, immune hemolysis, and parasitic infections (e.g., malaria and babesiosis). Ineffective erythro poiesis occurs in cobalamin, folate, and iron deficiencies. Resorption increased hemoglobin release and overproduction of bilirubin. In the absence of hemolysis, the physician should consider a problem with the hepatic uptake or conjugation of bilirubin.

Hematologic disease

Myeloid Hemoglobinopathies (congenital abnormality of the hemoglobin molecule or of the rate of hemoglobin synthesis) Sickle cell disease Thalassemia Methemoglobinemia Anemias (lack of red blood cells or hemoglobin) Iron-deficiency anemia Megaloblastic anemia Vitamin B12 deficiency Pernicious anemia Folate deficiency Hemolytic anemias (destruction of red blood cells) Genetic disorders of RBC membrane Hereditary spherocytosis Hereditary elliptocytosis Congenital dyserythropoietic anemia Genetic disorders of RBC metabolism Glucose-6-phosphate dehydrogenase deficiency (G6PD) Pyruvate kinase deficiency Immune mediated hemolytic anemia (direct Coombs test is positive) Autoimmune hemolytic anemia Warm antibody autoimmune hemolytic anemia Idiopathic Systemic lupus erythematosus (SLE) Evans syndrome (antiplatelet antibodies and hemolytic antibodies) Cold autoimmune hemolytic anemia Cold agglutinin disease Paroxysmal cold hemoglobinuria (rare)

Anemia

Anemias of increased red blood cell destruction are generally classified as hemolytic anemias. These types generally feature jaundice, and elevated levels of lactate dehydrogenase. Intrinsic (intracorpuscular) abnormalities cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic disorders. Hereditary spherocytosis is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleen. Hereditary elliptocytosis is another defect in membrane skeleton proteins. Abetalipoproteinemia, causing defects in membrane lipids Enzyme deficiencies Pyruvate kinase and hexokinase deficiencies, causing defect glycolysis Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetase deficiency, causing increased oxidative stress Hemoglobinopathies Sickle cell anemia Hemoglobinopathies causing unstable hemoglobins Paroxysmal nocturnal hemoglobinuria

First_Aid_Step2

Erythrocytosis (an abnormal elevation of hematocrit) may be either 1° (due to ↑ RBC production) or 2° (due to ↓ plasma volume and hemoconcentration). T AB LE 2.7 -5. Differential Diagnosis of Thalassemias β-thalassemia major 0/2 β Patients develop severe microcytic anemia in the frst year of life and need chronic transfusions or marrow transplant to survive. β-thalassemia minor 1/2 β Patients are asymptomatic, but their cells are microcytic and hypochromic on peripheral smear. Hydrops fetalis 0/4 α Patients die in utero. Hemoglobin H disease 1/4 α Patients have severe hypochromic, microcytic anemia with chronic hemolysis, splenomegaly, jaundice, and cholelithiasis. The reticulocyte count elevates to compensate, and one-third of patients have skeletal changes due to expanded erythropoiesis. α-thalassemia trait 2/4 α Patients have low MCV but are usually asymptomatic. Silent carrier 3/4 α Patients have no signs or symptoms of disease.

The classic triad of jaundice, anemia, and splenomegaly is rare in neonates. The most common finding in this population is jaundice. Thus hereditary spherocytosis should be considered in neonates with hyperbilirubinemia of unknown cause. Additionally, spherocytes are seen less often in newborns along with several markers of the hemolysis that are typically present in older infants or adults. [9] Most neonates with hereditary spherocytosis have a positive family history; this should increase suspicion and aid in the diagnostic workup of patients with an unknown cause of jaundice. [9]

[Hereditary spherocytosis: clinical characteristics and treatment with splenectomy].

To analyse the clinico-biological characteristics at diagnosis, the clinical course, and the response to splenectomy of a series of patients with hereditary spherocytosis (HS). The clinical records of 61 patients diagnosed of HS along 30 years were reviewed. The diagnosis was based upon the existence of family history, physical findings, blood cell examination, reticulocyte count, peripheral blood spherocytes, red-cell osmotic fragility, auto-haemolysis, serum haptoglobin, LDH, non-conjugated bilirubin and direct anti-human globulin test. Data regarding the time of diagnosis and clinical course were taken into account in every case. Within the sub-group of 29 patients undergoing splenectomy, the changes in haemoglobin rates and reticulocyte and platelet counts after surgery were evaluated. Of the 61 patients, 35 were men and 26 women; the median age at diagnosis was 13 years (range: 0-64 years). Family history was positive in only 40% of the cases. The mean haemoglobin rate was 112 g/L (range: 46-151 g/L), over 60% of the patients having anaemia. The mean reticulocyte count was 282 x 10(9)/L (range: 31-583 x 10(9)/L), this being above 100 x 10(9)/L in 91% of the cases. Red-cell osmotic fragility with fresh blood was increased in 86% of the cases, and in 97% after blood incubation. Serum haptoglobins were decreased, whereas LDH was increased in 58% of the patients and non-conjugated bilirubin in 72%. Splenomegaly appeared in the clinical course in 87% of the patients; cholelithiasis was present in 31.5% of them. Haemoiytic crises were seen in 45% of patients, aplastic phases in 7%, and transfusion was needed by 16% of the patients to variable extents. Splenectomy was performed in 50% of the instances before 14 years of age (range: 4-64 years), and it increased haemoglobin rates in 40 g/L, anaemia being corrected in all cases; the mean reticulocyte count returned to normal, but thrombocytosis developed after surgery, it being present in 82% of the cases 2-3 months later. (1) Wide clinical variability is seen in HS, from severe forms requiring frequent transfusion to asymptomatic cases. (2) Highly frequent findings in HS are reticulocytosis and splenomegaly; relatively frequent were anaemia, haemolytic crisis and cholelithiasis, in this order. (3) Anaemia was always corrected after splenectomy, which also rose the haemoglobin rate even in the cases without anaemia, and returned the reticulocyte count to normal values.

InternalMed_Harrison

The diagnosis of β-thalassemia major is readily made during childhood on the basis of severe anemia accompanied by the characteristic signs of massive ineffective erythropoiesis: hepatosplenomegaly, profound microcytosis, a characteristic blood smear (Fig. 127-5), and elevated levels of HbF, HbA2, or both. Many patients require chronic hypertransfusion therapy designed to maintain a hematocrit of at least 27–30% so that erythropoiesis is suppressed. Splenectomy is required if the annual transfusion requirement (volume of RBCs per kilogram of body weight per year) increases by >50%. Folic acid supplements may be useful. Vaccination with Pneumovax in anticipation of eventual splenectomy is advised, as is close monitoring for infection, leg ulcers, and biliary tract disease. Many patients develop endocrine deficiencies as a result of iron overload. Early endocrine evaluation is required for glucose intolerance, thyroid dysfunction, and delayed onset of puberty or secondary sexual

List of MeSH codes (C18)

– lactose intolerance – mannosidase deficiency diseases – alpha-mannosidosis – beta-mannosidosis – mucolipidoses – mucopolysaccharidoses – mucopolysaccharidosis I – mucopolysaccharidosis II – mucopolysaccharidosis III – mucopolysaccharidosis IV – mucopolysaccharidosis VI – mucopolysaccharidosis VII – multiple carboxylase deficiency – biotinidase deficiency – holocarboxylase synthetase deficiency – pyruvate metabolism, inborn errors – Leigh disease – pyruvate carboxylase deficiency disease – pyruvate dehydrogenase complex deficiency disease – cytochrome-c oxidase deficiency – glucosephosphate dehydrogenase deficiency – hyperbilirubinemia, hereditary – Crigler–Najjar syndrome – gilbert disease – jaundice, chronic idiopathic – lipid metabolism, inborn errors – hypercholesterolemia, familial – hyperlipidemia, familial combined – hypercholesterolemia, familial – hyperlipoproteinemia type IV – hyperlipoproteinemia type III

[Clinical and experimental studies of adult hereditary spherocytosis].

To explore the clinical characteristic of adult hereditary spherocytosis (HS) and the efficacies of splenectomy. Six cases with adult HS were collected from July 2006 to July 2012. And their clinical features, laboratory profile and treatment were retrospectively analyzed. There were 2 males and 4 females with a diagnostic age of 21-67 years. Their chief complaints were symptoms of upper gastrointestinal tract. The characteristic tetralogy was anemia, hemolysis, splenomegaly and gallstone.Familial inheritance pattern was found in 2 patients. The laboratory examination results demonstrated anemia, reticulocyte and elevated indirect bilirubin in 6 patients. Three patients had positive urobilinogen. The osmotic fragility (OF) test were 2 positive and 4 negative ones. And 2 negatives turned positive after incubation. The acidified glycerol lysis test (AGLT50) was positive in all. Ultrasonography showed splenomegaly and gallstone. There were 3 abnormal types red cells in peripheral blood, densely-dyed red cells (35%-89%) , microspherocytes (14%-20%) and irregular-shaped red cells.Scanning electron microscope showed single or many acanthocytes or spikes in red cell surface.Red cell body was irregular dish or flower-shaped. Biconcave disc shape disappearance. Three patients had short bands 3, 4.1 or 4.2. The age of onset was late and clinical symptoms was lighter.Spectrin-ankyrin was deficient for another 2 patients. The age of onset was early and clinical sign serious.Splenectomy and cholecystectomy were performed in 3 patients. Their postoperative hemoglobin was normal during follow-ups. Clinical relief was achieved. Combined experiments can enhance the diagnostic rate of adult HS so as to avoid misdiagnosis. And the efficacies of splenectomy are definite.

Unconjugated Hyperbilirubinemia -- History and Physical

Patients with unconjugated hyperbilirubinemia may present with jaundice or other signs, or the condition may be noticed in the asymptomatic patient by the finding of high levels of bilirubin in the serum during routine blood testing. As far as the differential diagnosis of unconjugated hyperbilirubinemia is involved, it requires a detailed history and physical examination of patients for the evaluation. The assessment of the patient’s clinical history includes; age at the disease manifestation, ethnic origin/race, hereditary disorder, family history of anemia or jaundice, recently used medications, diet history, and history of liver disease.

Neonatal jaundice

Unconjugated Hemolytic Intrinsic causes of hemolysis Membrane conditions Spherocytosis Hereditary elliptocytosis Enzyme conditions Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency) Pyruvate kinase deficiency Globin synthesis defect sickle cell disease Alpha-thalassemia, e.g. HbH disease Extrinsic causes of hemolysis Systemic conditions Sepsis Arteriovenous malformation Alloimmunity (The neonatal or cord blood gives a positive direct Coombs test and the maternal blood gives a positive indirect Coombs test) Hemolytic disease of the newborn (ABO) Rh disease Hemolytic disease of the newborn (anti-Kell) Hemolytic disease of the newborn (anti-Rhc) Other blood type mismatches causing hemolytic disease of the newborn

[Clinical and genetic features of children with hereditary spherocytosis: an analysis of 4 cases].

Four children (two boys and two girls), aged from 3 years and 7 months to 5 years, had mild or moderate anemia, mild hepatosplenomegaly, jaundice (mainly an increase in indirect bilirubin), an increase in the percentages of reticulocytes and spherical erythrocytes in peripheral blood smear and an increase in erythrocyte osmotic brittleness. High-throughput sequencing found two novel mutations in the SLC4A1 gene, c.37G>A and c.340T>C, in case 1 and case 2 respectively, and these two mutations were predicted to be pathogenic by Mutation Taster. The Polyphen2 scores of these two mutations were 0.87 and 0.83 respectively, which suggested that these mutations were probably damaging. The SIFT scores of these two mutations were 0.008 and 0.09 respectively, suggesting that these mutations were probably damaging. No abnormality in this gene was found in their parents. Two reported heterozygous mutations in the ANK1 gene, c.830A>G and c.985G>C, were found in case 3 and case 4 respectively. Gene detection was not performed for the parents of case 3. The mother of case 4 was diagnosed with hereditary spherocytosis and had a heterozygous mutation of c.985G>C in the ANK1 gene. All four children were diagnosed with hereditary spherocytosis. Case 3 had a hemoglobin level of <80 g/L and underwent splenectomy at the age of 5 years and 6 months, and regular postoperative reexamination showed a hemoglobin level of >105 g/L. Hereditary spherocytosis is a hereditary hemolytic disease caused by abnormality in erythrocyte membrane protein, and gene detection helps to make a confirmed diagnosis.

InternalMed_Harrison

dispute this assertion. Moreover, on theoretical grounds, the results of such studies should provide no more information than simple measurements of the baseline serum bilirubin concentration. Family studies indicate that GS and hereditary hemolytic anemias such as hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, and β-thalassemia trait sort independently. Reports of hemolysis in up to 50% of GS patients are believed to reflect better case finding, since patients with both GS and hemolysis have higher bilirubin concentrations, and are more likely to be jaundiced, than patients with either defect alone.

Congenital hemolytic anemia

Congenital hemolytic anemia refers to hemolytic anemia which is primarily due to congenital disorders. Types Basically classified by causative mechanism, types of congenital hemolytic anemia include: Genetic conditions of RBC Membrane Hereditary spherocytosis Hereditary elliptocytosis Genetic conditions of RBC metabolism (enzyme defects). This group is sometimes called congenital nonspherocytic (hemolytic) anemia, which is a term for a congenital hemolytic anemia without spherocytosis, and usually excluding hemoglobin abnormalities as well, but rather encompassing defects of glycolysis in the erythrocyte. Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism) Pyruvate kinase deficiency Aldolase A deficiency Hemoglobinopathies/genetic conditions of hemoglobin Sickle cell anemia Congenital dyserythropoietic anemia Thalassemia See also Hematopoietic ulcer List of circulatory system conditions References External links Hereditary hemolytic anemias

Clinico-hematological profile of hereditary spherocytosis: experience from a tertiary care center in North India.

Hereditary spherocytosis (HS) is an inherited membranopathy characterized by phenotypic and genotypic heterogeneity. This study describes the clinico-hematological profile of 70 HS patients diagnosed at a tertiary care center in North India over a period of five years. Patients commonly presented with intermittent jaundice (82.9%), pallor (80%) and dark colored urine (11.4%). The common signs were splenomegaly (92.9%), hepatomegaly (50%), cholelithiasis or choledocholithiasis (36.8%) and hemolytic facies (10%). Family history was contributory in 28.6% patients. Blood transfusion (BT) requirement was present in 35.7% patients. Unconjugated and conjugated hyperbilirubinemia was seen in 89.1 and 10.9% patients respectively. At presentation, the hemoglobin ranged from 3-14 g/dl with a mean of 9.37 g/dl (SD2.43). Spherocytes were seen in 88.6% and incubated Osmotic fragility test (OFT) was positive in 88.2% patients. The Eosin-5-maleimide (EMA) flow cytometric test was done in 28 patients. Mean fluorescence intensity (MFI) for normal subjects was 11861.5 (SD-883.51) and for confirmed HS patients was 7949.3 (SD1304.1). Taking the MFI range of 5341.1-10 557.5 for HS, eight cases of suspected HS/undiagnosed hemolytic anemia with a negative (n=5) or equivocal (n=3) incubated OFT were diagnosed as HS. An increase in HbF level was seen in 10 cases ranging from 2.1 to 17.7% with a mean of 5.66%, three of these had associated beta thalassaemia trait. Twelve patients (17%) underwent splenectomy and 91% of them did not require any BT post-splenectomy. Among the patients treated conservatively 49% had persisting pallor and 16.3% had transfusion requirement.

Hemolysis

Toxic agent ingestion or poisoning Paxillus Involutus ingestion can cause hemolysis. Intrinsic causes Hemolysis may result from intrinsic defects in the red blood cell itself: Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis) Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia) Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency) Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia. Extrinsic causes

Hereditary spherocytosis.

A 12-year-old girl was brought to the Dhaka Hospital of ICDDR,B with diarrhoea. Incidentally, the parents provided a history of repeated episodes of pallor and jaundice since she was two and half years old. Three of her family members had similar problems. History, clinical examination, and laboratory findings of the girl and her family members suggested a case of hereditary spherocytosis. To our knowledge, this is the first report of such a case in Bangladesh.