Unknown unknowns for Hepatitis C

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“ [T]here are known knowns; there are things we know that we know.
There are known unknowns; that is to say there are things that, we now know we don’t know.
But there are also unknown unknowns – there are things we do not know, we don’t know.		 ”
—United States Secretary of Defense, Donald Rumsfeld February 2002

Reading a recent epidemiology article reminded me of the preceding referenced quote  (Hepatology 2012; 55: 1652-61).  This study took a close look at knowledge of being infected with hepatitis C virus (HCV) and what HCV infection may indicate.

The study identified 30,140 participants through the National Health and Nutrition Examination Survey (NHANES) conducted from 2001-2008.  The Centers for Disease Control (CDC) obtains nationally representative data on the health and nutritional status of noninstitutionalized civilians across the U.S.  NHANES uses a ‘complex, stratified, and mulitstage probability sampling design and collects information from approximately 5,000 persons per year using standardized household interviews, physical examinations, and testing of biologic samples.’

Participants 6 years of age or older who tested positive for anti-HCV antibodies were sent a report.  Out of the 30,140 participants, 393 (1.4%) had evidence of past or current HCV infection; 170 were available for the study investigators.  Only 49.7% were aware of HCV status prior to receiving NHANES letter.  Furthermore, only 3.7% were first tested for HCV because they or their doctor thought they were at risk for infection; most were tested as part of a routine exam (perhaps detected after elevated ALT values) (46.7%), due to symptoms (15.9%), or blood donation (9.7%).

Another aspect of the study was determining the participants’ understanding of HCV infection.  Correct responses to the HCV survey were more likely in individuals between 40-59 years of age, white non-Hispanics, and patients who had seen a doctor about their HCV infection.  Specific questions often answered incorrectly included the following:

  • whether HCV could be contacted by kissing –only 68% knew this was false
  • whether HCV could be transmitted sexually –only 64% knew this was true
  • whether HCV could be acquired during birth if mother had HCV –only 57% knew this was true

Take home points:

  • Risk-based screening for HCV will continue to fail.  Physicians may not elicit adequate information and patients may deny risky behaviors even if asked.
  • Approximately half of patients in this cohort were unaware of HCV infection.
  • Many misconceptions about HCV persist even among those who had received counseling.

Related blog posts:

Pediatric HCV Guidelines

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Additional resource:

http://www.cdc.gov/hepatitis/RiskAssessment/  This website allows individuals to assess their risk for hepatitis.

TODAY is worrisome for a lot of tomorrows

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The TODAY study (NEJM 2012; 366: 2247-56 and editorial 2315-16) =Treatment Options for Type 2 Diabetes in Adolescents and Youth.

While the study has a catchy acronym, the findings are disturbing.  Eligible patients (n=699) were 10 to 17 years old were followed on average over 3.86 years; they were divided into three groups:

  • Metformin 1000mg BID –48% achieved primary outcome (glycated hemoglobin <8% for at least 6 months).
  • Metformin with lifestyle changes –53% achieved primary outcome.  The lifestyle counseling that patients received in the study likely exceeded the typical counseling that most patients receive in clinical practice.
  • Metformin with rosiglitazone (4mg BID) –61% achieved primary outcome.  While this group had the best glycemic response, this group also had the greatest increase in BMI.

Other findings:

Comorbid conditions were common:

  • Hypertension: at baseline in 81 (11.6%) and new cases during study 155 (22.2%)
  • Dyslipidemia (LDL): at baseline in 23 (3.3%) and new cases during study 49 (7%)
  • Triglyceridemia: at baseline in 127 (18.2%) and new cases during study 70 (10%)
  • Microalbuminurina: at baseline in 44 (6.3%) and new cases during study 72 (10.3%)

Frequent adverse events noted with medications (Table 2 in study): gastrointestinal symptoms noted in about half of all study participants in each group, rash noted in about 40%, and elevated LFTs in about 40%.

Take home messages (borrowed from editorial):

“Most youth with type 2 diabetes will require multiple oral agents or insulin therapy within a few years after diagnosis”

“Fifty years ago, children did not avoid obesity by making healthy choices; they simply lived in an environment that provided fewer calories and included more physical activity.”

“Public-policy approaches–sufficient economic incentives to produce and purchase healthy foods and to build safe environments that require physical movement…will be necessary to stem the epidemic of type 2 diabetes and its associated morbidity.”

Related posts:

Treating diabetes with surgery

Cardiovascular disease for the entire family

Staggering cost of obesity

Lower leptin with physical activity

Reasons for refeeding syndrome

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Refeeding syndrome (RFS) is defined as the potentially fatal shifts in fluid and electrolytes that may occur in malnourished patients who are abruptly refed either enterally or parenterally.  The biochemical hallmark is hypophosphatemia.  Other changes can include hypokalemia, hypomagnesemia, and thiamin deficiency.  RFS can worsen the prognosis of children with celiac crisis as well (JPGN 2012; 54: 522-5).

A chart review from Lucknow, India from Jan-Dec 2010, identified 5 cases of RFS among 35 celiac patients.  All were severely malnourished.  All had anemia, hypoalbuminemia, hypophosphatemia, hypokalemia, and hypomagnesemia.  All improved with initial caloric restriction followed by gradual escalation of caloric intake along with electrolyte supplementation.

This article shows that a variety of causes of malnutrition can lead to refeeding syndrome. Considering refeeding syndrome in any severely malnourished child may help improve the prognosis by altering the nutritional management.

Additional references:

  • Nutr Clin Pract 2012; 27: 34-40. Reviewed refeeding syndrome publications since 2000.  Hypophosphatemia occurred in 96% of cases (26 of 27).
  • Crit Care Med 2010; 14: R172-R178.  Refeeding syndrome with anorexia.
  • Nutrition 2010; 26: 156-67. Review of refeeding syndrome treatment.
  • Nutr Clin Pract 2008; 23: 166-71.  Death due to refeeding syndrome.
  • JPEN 1990: 14.1; 90-97. Refeeding syndrome review.
  • Crit Care Med 1990; 18: 1030-1033. Review.

Pediatric HCV Guidelines

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A useful recent article, ‘NASPGHAN Practice Guidelines for pediatric HCV’ (JPGN 2012; 54: 838-55) needs to be a handy reference.  However, given the rapid changes in the HCV field, it is likely that this reference will need to be updated soon to incorporate new information (eg. IL28b) as well as emerging therapies.

Highlights:

Epidemiology: 0.2% of children & 0.4% of adolescents are HCV-infected; primary mode is mother to child (vertical) transmission which occurs in 5-7% if mother not coinfected with HIV

Testing: For infants of HCV-infected mothers, check HCV antibody after 18 months or HCV RNA at younger ages.  Need two negative HCV RNAs to exclude infection (guidelines suggest checking 6 months apart).  Most individuals should be screened with antibody testing and confirmed with RNA test.

Screening for HCC (U/S, AFP): suggested only “for those with significant liver disease (ie. cirrhosis)” due to rarity of HCC in pediatric HCC.

Treatment:

  • Not if patient younger than 3 years
  • Probably Pegylated-interferon with ribavirin –references for pediatric studies indicate response rates of about 50% for genotype 1 and about 80% for types 2 & 3.
  • Who should be treated? Not always clear.  Probably those with elevated aminotransferases or progressive disease based on liver biopsy.  Possibly those with mild disease to eradicate virus.
  • Dosing: ribavirin  15/kg/day divided twice daily; weekly PEG-IFN-α-2a 180 microgram/1.73 m2 or weekly PEG-IFN-α-2b 60 microgram*m2

Treatment monitoring (Table 8):

  • CBC/diff, Hepatic panel, glucose 0, 1, 2, 4, 8, 12 weeks, then every  4-8 weeks
  • T4/TSH 0, 12, 24, 36, 48 weeks
  • Urine HCG 0, 24 weeks (if female >12 years)
  • Prothrombin, Urinalysis at week 0
  • HCV RNA 0, 24, 48, 72 weeks

Anticipatory Guidance: “no legal requirement” to disclose HCV infection in U.S.; however, CDC suggests revealing this information to sexual partners (http://www.cdc.gov/hepatitis/hcv/)

  • Avoid sharing toothbrush, shaving equipment with household contacts, unprotected sexual activity with multiple partners, tattooing/piercing
  • Do not need to screen household or casual contacts

Special issues:

  • Vaccines: HCV patients should receive all standard vaccines
  • Obesity and alcohol both can worsen the outcome
  • Fetal scalp probes and prolonged rupture of membranes but not route of delivery may increase risk of HCV transmission
  • Breastfeeding is not contraindicated but should be avoided during mastitis/bleeding

Additional related blog links:

HCV now more deadly than HIV

The cost of progress in treating Hepatitis C

Increased ferritin predicts poor response in Hepatitis C

Curing Hepatitis C without interferon

Looking for trouble

Additional references:

  • –Hepatology 2011; 54: 1433. AASLD guidelines.  See teleprevir & boceprevir as well.-http://www.aasld.org/eweb/docs/hepatitisc
  • -Hepatology 2011; 53: 1468. PEG/RBV have minimal effect on QOL/cognitive/emotional outcomes, n=114.
  • -Gastroenterology 2011; 140: 389, 450-58. HEP-C STUDY. Comb RBV (15mg/kg div BID) & PEG-2a (180mcg/1.73m2 body surface q week) is better than PEG monotherapy. 53% SVR in combo group. Neutropenia in 40% –needed to reduce dose see below). “The Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents With Chronic Hepatitis C.”
  • -Hepatology 2009; 49: 1335. Comprehensive review and guidelines
  • -J Hepatology 2010; 52: 501-07. n=107. Pediatric study. Wirth et al. Efficacy of PEG alfa-2b (1.5/g/d) & RBV (15/kg/day): Genotypes 2/3 96% SVR, genotype 1 55%.
  • -JPGN 2006; 43: 499.  Study of PEG-IFN-α-2a in children.  dose BSA m2/1.73 x 180microgm weekly x 48 weeks.  6/14 (43%) had sustained response.  all genotype 1.  Article states that IFN (3/week) + RBV has now been approved by FDA for those over 3 years

PEG-Interferon Dosing:

Dosing adjustment from hep C study in children –needed in ~40%

PEG -2a
original: 180mcg/1.73m2
1. level 1: 135 mcg, level 2: 90mcg, level 3: 45 mcg

If ANC 750-999 week 1-2: level 1 adjustment, weeks >3: no adjustment
If ANC 500-749: week 1-2: hold dose ’til >750, then level 1; weeks >3, level 1 adjustment
If ANC 250-499: week 1-2, hold until >750, then level 2 adjustment, weeks >3, then hold ’til 750, then level 1 adjustment
If ANC <250, stop drug

If PLTs 35-49K, hold til >50, then level 1
If PLTs 25-34, hold til >50, then level 2
If PLTs <25, stop drug

If Hgb <10, reduce RIBA dose by 1/2 & increase dose when hgb>10
If hgb <8.5, stop RIBA

If indirect bili >5, stop drug.  If <2.5, restart dose at one-half and if remains less than 2.5, can resume full dose after 4 weeks.

IF ALT 5-10 ULN, recheck in 1 week.  If stays high, level 1 adjustment.
IF ALT10 ULN for more than 1 week, then if drops to 5-10, level 1 but if remains >10 ULN, then stop drug.

Side effect frequency:
flu symptoms: 91%, h/a, 62%, GI symptoms 56%, injection pain 45%, muscle aches 36%, irritable 31%, fatigue 27%, rash 20%, itching 15%, anorexia 13%, trouble sleeping 11%, depression 4-12%

TNF-α antagonists and infections

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In our pediatric patients who receive tumor necrosis factor-α (TNF-α) antagonists, fortunately we see few infectious complications.  In older patients, infections are much more important source of morbidity.  The main TNF-α inhibitors in clinical use include infliximab, etanercept, adalimumab, and certolizumab. Two large studies help quantify this risk:

  • Grijalva CG et al. JAMA 2011; 306: 2331-39.
  • Strangeld A et al. Ann Rheum Dis 2011; 70: 1914-20.

The first study assembled retrospective cohorts between 1998-2007 with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis/psoriatic arthritis or ankylosing spondylitis (group 3).  This study’s acronym is SABER: Safety Assessment of Biologic Therapy. This data was compiled from 4 large US automated databases.  In total, there were 10,484 RA, 2323 IBD, and 3215 group 3 patients.  1172 serious infections were identified, mostly (53%) pneumonia or skin/soft tissue infections.  Among IBD patients, hospitalization rates were 10.91 (per 100 person-years) for TNF-α antagonists and 9.6 for comparison group.  The rates of hospitalization were similar in RA (8.16 with TNF-α antagonists) and lower in the group 3 patients (5.41 with TNF-α antagonists).   In all groups, baseline glucocorticoid use was associated with a dose-dependent increase in infections.  Overall, there was not an increase risk of hospitalizations with TNF-α antagonists compared with nonbiologic treatments.

The second cited reference examined patients from Germany with RA, enrolled in the RABBIT registry.  Data was available for 5044 patients.  There were 392 serious infections in this cohort with fewer infections noted after 3 years.  Risks for infection included age (>60), chronic lung or renal disease, history of serious infections, and treatment with glucocorticoids.  Treatment with 7.5-14mg conferred at relative risk (RR) of 2.1; treatment with ≥15mg conferred a RR of 4.7.  The rates of serious infections has an exponential change when risk factors are added together.  In Figure 3, estimated risk of serious infections for patients receiving ≥15mg  glucocorticoids along with three additional risk factors was 45% per year; with two risk factors the risk was approximately 20% and with one additional risk factor approximately 10%.

While these studies confirm significant risks of infections with biologic agents, the absolute risk is low particularly when other risk factors are not present.  In pediatric populations, glucocorticoids are the most prominent risk factor.  In addition, the risk of serious infections may be reduced by effective therapy.  In the SONIC study, serious infectious complications were less frequent in patients on combination therapy (infliximab and azathioprine) than with either monotherapy.  This result was likely due to the decreased need for glucocorticoids.

Additional references/relevant previous blogs:

  • NEJM 2010; 362: 1383. Sonic study. Combination AZA/IFX with greater efficacy. 56.8% remission in combo Rx.
  • -IBD 2008; 14: 721.  Pneumocystis jiroveci (carinii) w infliximab -review of 84 cases.  Dig Dis Sci 2007; 52: 1481-84.  PCP most likely to occur on average 3 weeks after 2nd infusion (possibly due to concommitant drug use)
  • -Gastroenterology 2008; 134: 929.  n=100 consecutive IBD patients with opportunistic infections.  Any of drugs associated w ~2.9 OR in adutls (greatest in >50yrs).  OR 14.5 when multiple immune drugs. Steroids more associated with Candida. AZA/6MP more with viral: HSV, VZV (shingles), CMV.  IFX less commonly with infections -though increased histoplasma and atypical mycobacterium
  • -Gastroenterology 2009; 136: 1182.  Review of biologics.
  • -IBD 2007; 13: 769.  Review of safety of wide range of biologics
  • –Clin Gastroenterol Hepatol. 2006; 5:621-30.  TREAT registry.  Steroids but not biologics associated with increased mortality risk.
  • Only one chance to make first impression

Look of improvement on an EoE diet

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In this month’s Gastroenterology, 50 adults with Eosinophilic esophagitis (EoE) were treated with a 6-food elimination diet (SFED) (Gastroenterology 2012; 142: 1451-1459).  Repeat endoscopy after 6 weeks determined responsiveness.  Histologic response was defined by having <5 eosinophils/high power fields (eos/hpf).  In 20 patients, reintroduction of foods followed by repeat endoscopy was undertaken.

After SFED, 32 (64%) had peak eosinophil counts <5 eos/hpf.  Symptom scores decreased in 94%.  After trigger food reintroduction, eosinophil counts returned to pretreatment values.  The changes are clearly visible in Figure 5.  The pictures are almost like the weight loss commercials on TV –striking improvement.  I contemplated putting in a scan of the Gastroenterology cover, but have not received permission from the publisher.  Check out this link to view it yourself:

http://download.journals.elsevierhealth.com/pdfs/journals/0016-5085/PIIS0016508512006257.pdf

Based on reintroduction, the foods most commonly associated with EoE were wheat (60%), and milk (50%).  Skin-prick testing predicted only 13% of foods associated with EoE.  In general, these study results mirror results from pediatric studies, with the exception that milk allergy has been found to be more common in some pediatric studies.

Only 20 patients completed the reintroduction process.  This process involved adding 1 food group every 2 weeks.  If the patient had symptoms during reintroduction or remained on regimen for 4 weeks, then  endoscopy with biopsies was performed.  If recurrence noted based on symptoms or histology, this required a 6 week washout before additional food reintroduction.  Of note, median time for recurrence of symptoms was 3 days after reintroduction.

Six foods: milk, wheat, eggs, soy, shellfish/fish, nuts.

This study shows that, as in children, adult EoE is predominantly a food-allergy disease

Related blog entries:

Eosinophilic Esophagitis -Six Food Group Diet

Guidelines for Eosinophilic Esophagitis

MicroRNA signature for eosinophilic esophagitis

The undiscovered country

Upper endoscopy useful for identifying Crohn’s disease

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In a large pediatric study, the value of upper endoscopy in detecting Crohn’s disease (CD) is evident (JPGN 2012: 54: 753-57).

While the majority of pediatric patients with suspected inflammatory bowel disease probably undergo both upper endoscopy and colonoscopy, the added value of upper endoscopy remains unclear.  In this retrospective study with 171 pediatric patients (70 with CD, 33 with UC, 68 Non-IBD), 11% of children with CD had the diagnosis established based “solely” on the finding of granulomatous inflammation in upper intestinal tract (along with clinical symptoms).

Other key findings:

  • Presence of histologic gastric inflammation in CD patients compared to control patients was significantly higher (p<0.0001) but not significantly higher compared to UC patients (p=0.19).
  • Duodenal inflammation was highly suggestive of CD compared with both UC and non-IBD patients.  This occurred in 19% of CD patients compared with 0% and 1% in the other groups respectively.
  • 21 children (30%) had granulomas identified in upper GI tract (19 in stomach).  In 8 (11%), the diagnosis was changed based on this finding.  Prior to histology, the tenative diagnosis: 2 UC, 4 IC, 2 non-IBD.
One curious finding was a the presence of “perianal abscess/fistula” with similar frequency in CD patients and UC patients based on their Table 2 Patient Characteristics.
Additional references:
  • -IBD 2009; 15: 1101-4.  Presence of UGI disease in IBD.
  • -JPGN 2007; 44: 653.  NASPGHAN report on discriminating/labelling UC vs. Crohn’s.
  • -JPGN 2002; 35: 636-40. Advocates panendoscopy for all new IBD.  Granulomas in 28% of EGDs & 71% of UC pts c some abnl on EGD; 82% Crohn’s c abnl EGD.
  • -JPGN 2005; 41: abstract 181 (page 549).  UGI identified granulomas in 15% that were not identified elsewhere.
  • -JPGN 2004; 39: 257-61. Diagnostic role of EGD for pediatric IBD.
  • Magnetic resonance enterography for Crohn’s disease

HAV vaccination: how long will it take?

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Despite the availability of a safe and effective vaccine, immunization rates in the U.S. remain poor (Pediatrics 2012; 129: 213-221).

In this study which included data from the 2009 National Immunization Survey-Teen, hepatitis A virus (HAV) vaccination  coverage was examined in adolescents 13-17 years of age.  The national coverage for at least 1 dose was 42%; 70% of these vaccinees completed the 2-dose series.  For Georgia, the rates were similar to national data: the 1-dose receipt % was 42.5% and the 2-dose receipt % was 26.3%; 62% completion of 2 doses.

More specific breakdown of coverage rates:

  • 74.3% from 11 states that recommended universal HAV vaccination since 1999
  • 54% from 6 states that recommended consideration of HAV vaccination since 1999 & universal coverage since 2006
  • 27.8% for 33 states that recommended universal vaccination since 2006

While acute HAV rates have been declining, in 2009 there were 1987 reported cases; the CDC estimates that the total number of cases was 21,000 (due to underreporting and asymptomatic cases).  The highest rates of disease were in young adults between 20-29 years of age.

This data is disappointing. Yet, extrapolation from this data indicates that national coverage in seven years, when all states will have had 10 years to implement universal vaccination to young children, could be markedly better.

Additional references:

  • -NEJM 2007; 357: 1685. HAV vaccine effective in preventing cases of HAV after exposure (as good as IVIG). Low rates of HAV c postexposure prophylaxis c HAV vaccine (4.4%) or immune globulin (3.3%). n=1090.
  • -MMWR 2007; 56: 1080-84. Updated recs for IVIG -use only for exposures in infants <12months, immunocompromised persons, persons with chronic liver disease, or persons w contraindications to HAV vaccine.
  • -Pediatrics 2007; 120: 189. Recs from AAP. Recs for vaccine — all children at 1 year of age in US w 2-dose regimen; w/in 1 mo of 1st dose 97% of children & 95% of adults develop protective antibody. VAERS (adverse rxns) 800-822-7967 for forms.
  • -Pediatrics 2007; 119; e12, e22. HAV vaccine is cost-effective.
  • -MMWR 2007; 56: No. SS-3. drop in new infections by 80% compared to previous nadir; HAV 1.5/100,000 & HBV 1.8/100,000
  • -Hepatology 2006; 44: 1589. Decreasing incidence of fulminant HAV ; between 1988-2005, decrease of HAV in UNOS database from 0.7% to 0.1%. Risk factors for severe disease: creatinine >2, ALT <2600, intubation, pressors.
  • -J Pediatr 2004; 144: 327. Maternal antibody decrease HAV vaccine response when administered at 2, 4 & 6 months.
  • -Am J Gastroent 2002; 97: 721-8. ? cost-effective to vaccinate HCV pts; however, ~35% FHF risk if secondarily infected.

Test your knowledge of Clostridium difficile

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While Clostridium difficile (C diff) is a common infection, there is a lot to know.  A thorough but brief review is a good place to test your knowledge (Clin Gastroenterol Hepatol 2012; 10: 581-92).

  • a. When was C diff discovered?
  • b. When was C diff identified as a cause of antibiotic-associated diarrhea?
  • c. What antibiotics have been associated with a surge in severity and frequency of C diff infections?
  • d. Which C diff strains are the predominant cause of severe C diff?
  • e. How many C diff infections are occurring yearly in hospitalized patients in U.S.?
  • f. What are the most important risk factors?
  • g. How does the risk profile change for multiple antibiotics?
  • h. What time of year sees the greatest number of infections?
  • i. What does C diff smell like?
  • j. What % of antibiotic-associated diarrhea is due to C diff?
  • k. What clinical parameters may indicate severe infection and which ones indicate fulminant infection?
  • l. How much does a nucleic acid amplification test (NAAT) cost compare to enzyme immunoassay (EIA)?  How does this test work? What are the advantages/disadvantages?
  • m. How to treat severe infection?
  • n. What instructions should be given to prevent C diff in hospital?

Answers:

  • a. 1935
  • b. 1970s
  • c. Fluoroquinolones
  • d. BI/NAP1/027.  This strain has hypersecretion of toxins A & B, the presence of binary toxin, and resistance to fluoroquinolones.
  • e. CDI present in 300,000 hospitalized patients in 2005 (vs. 85,000 in 1993)
  • f. Hospitalization, older age (>65 years), and receipt of antibiotics (especially during 1st two months).
  • g. Hazard ratio 2.5 for two antibiotics, HR 9.6 for exposure to five antibiotics
  • h. Winter
  • i. “Horse stable”
  • j. 15-25%
  • k. Severe: WBC>15,000, Creatinine >1.5 fold patient’s baseline.  Also, albumin <2.5, admission to ICU, pseudomembranes on endoscopy, comorbid diseases.  Fulminant: (50% mortality) colon >6cm in diameter/toxic megacolon, WBC >50,000, lactate >5 mmol/L.
  • l. ~10 times the cost.  Works by identifying genes that encode toxins by PCR or loop-mediated amplification of DNA.  Test is very sensitive and rapid but may have false-positives.  Some recommend using a less expensive test for screening to decrease costs.
  • m. Vancomycin up to 500mg QID (NG/PO) plus metronidazole.  If complete ileus, vancomycin can be given rectally
  • n. Hand hygiene (not alcohol): either soap or chlorhexidine, contact precautions, cleaning environment –chlorine solutions effective (1000-5000 ppm), antimicrobial stewardship (especially reducing clindamycin and fluoroquinolones)

How many did you get right?

Related posts:

Clostridium difficile -Current Battlelines

Proton pump inhibitors–infection risk with cirrhosis

A cautionary vitamin D tale?

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A recent case report indicates that pharmacologic doses of vitamin D can cause hypercalcemia and hypervitaminosis D (Pediatrics 2012; 129: e1060-63).  The three cases all document good reasons for instituting therapy: craniotabes, hypocalcemic seizures, and tibial bowing.  The total dose that the patients received over 7-12 weeks ranged from 112,000 IU to 168,000 IU.  The ages of the patients ranged from 2 weeks to 33 months.   The peak abnormal calcium for all three patients was 11 mg/dL and the peak 25-hydroxy vitamin D was 102 ng/dL.  There were no clinical symptoms in these three patients due to increased calcium.  A fourth oh-by-the-way patient was described as well.  This patient was receiving vitamin D for an “inappropriate indication” (failure to thrive) and had received 3.6 million IU without monitoring.  This led to the development of a multitude of symptoms associated with a calcium level of 17.4 mg/dL.

My take-home points:

  • If giving generous doses of vitamin D, obtain a followup calcium several weeks into therapy. However, pharmacologic doses of vitamin D for valid indications pose a very low risk.
  • Excessive doses of vitamin D can be detrimental. (This last statement may be akin to the warning “hot coffee might cause a burn.”)

Related blog entries:

Common to be “D-ficient”

Vitamin D, IBD, and Causality