Leilani St. Anna, MLIS, AHIP

Evidence summary

The most commonly measured outcomes in allergic rhinitis and conjunctivitis trials are symptom scales, which are neither standardized nor clinically validated. Almost all the studies discussed here calculated outcomes as a percentage change from baseline symptom scores but didn’t provide absolute values, so it isn’t clear whether statistical differences are clinically relevant.

Steroids provide more relief of nasal symptoms
A meta-analysis of 21 randomized placebo-controlled trials (total 2821 patients, average age mid-30s) that compared changes in TNSS with intranasal steroids and oral antihistamines among adults with seasonal allergic rhinitis found that steroids reduced TNSS more than antihistamines.¹ Most of the patients had had moderate to severe symptoms for several years.

Investigators calculated percent changes from baseline in mean TNSS, which typically included sneezing, itching, congestion, and rhinorrhea, each usually scored on a scale of 0 to 3.¹ Individual RCTs compared one of 3 intranasal steroids (fluticasone, triamcinolone, or budesonide) and one of 3 oral antihistamines (cetirizine, loratadine, or fexofenadine) with placebo; no studies compared medications within classes against each other.¹

On individual symptom scores, intranasal steroids reduced sneezing, itching, congestion, and rhinorrhea more than placebo by more than 20%. Both intranasal steroids and oral antihistamines decreased itching and rhinorrhea a similar amount, but antihistamines reduced congestion by only 5% to 10% more than placebo.¹

This meta-analysis included only studies reporting TNSS as an outcome, and individual studies used varying TNSS scales. Investigators attributed heterogeneity in the studies to intraclass differences between medications.¹

Two drug company-sponsored RCTs (1616 patients combined, average age 30s, moderate to severe allergic rhinitis) published before the meta-analysis also demonstrated that the intranasal steroid fluticasone propionate modestly reduced TNSS compared with the oral antihistamine fexofenadine (1 point vs 1.3 on a scale of 0 to 12).² TABLE 1 summarizes the results of studies comparing intranasal steroids and oral antihistamines to reduce nasal symptoms.

TABLE 1
Intranasal steroids vs oral antihistamines for nasal symptom relief

Results for eye symptoms are mixed
A meta-analysis of 11 RCTs (1317 patients, average age 32) showed no significant difference in relief of eye symptoms between oral antihistamines (dexchlorpheniramine, terfenadine, and loratadine) and intranasal steroids (budesonide, beclomethasone, fluticasone, and triamcinolone) in patients with seasonal allergies, as measured by various symptom scores.³

Three other studies indicated that intranasal steroids (triamcinolone, fluticasone) relieved eye symptoms more effectively than oral antihistamines (loratadine, fexofenadine) based on mean reductions in TNSS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Total Ocular Symptom Score (TOSS).^4-6 Of these scoring systems, only the RQLQ has been clinically validated.⁷

One additional study (including 2 RCTs) showed conflicting results.² TABLE 2 summarizes the results of studies comparing intranasal steroids and oral antihistamines to relieve eye symptoms.

TABLE 2
How intranasal steroids compare with oral antihistamines for reducing eye symptoms

Antihistamines cost less than steroids and are available OTC
Oral antihistamines are less expensive than intranasal steroids and are available over the counter. The cost of antihistamines ranges from $5.70 to $21.99 for a month of treatment, whereas the cost of intranasal steroids for the same period varies from $60.99 to $149.99.⁸

In the studies reviewed here, the 2 interventions showed similar harms, including sore throat, epistaxis, and headache.^2,4-6

Recommendations

The American Academy of Allergy, Asthma and Immunology’s 2010 guidelines conclude that intranasal steroids are first-line treatment for allergic rhinitis. If the patient prefers, use oral antihistamines.⁹

The Joint Task Force on Practice Parameters for Allergy and Immunology also recommends intranasal steroids as the most effective medication class for treating allergic rhinitis; no drug within the class is preferable to another. Daily administration is more effective than administration as needed, although the latter is an option. For treating ocular symptoms, intranasal corticosteroids and oral antihistamines work equally well.¹⁰

Evidence summary

The most commonly measured outcomes in allergic rhinitis and conjunctivitis trials are symptom scales, which are neither standardized nor clinically validated. Almost all the studies discussed here calculated outcomes as a percentage change from baseline symptom scores but didn’t provide absolute values, so it isn’t clear whether statistical differences are clinically relevant.

Steroids provide more relief of nasal symptoms
A meta-analysis of 21 randomized placebo-controlled trials (total 2821 patients, average age mid-30s) that compared changes in TNSS with intranasal steroids and oral antihistamines among adults with seasonal allergic rhinitis found that steroids reduced TNSS more than antihistamines.¹ Most of the patients had had moderate to severe symptoms for several years.

Investigators calculated percent changes from baseline in mean TNSS, which typically included sneezing, itching, congestion, and rhinorrhea, each usually scored on a scale of 0 to 3.¹ Individual RCTs compared one of 3 intranasal steroids (fluticasone, triamcinolone, or budesonide) and one of 3 oral antihistamines (cetirizine, loratadine, or fexofenadine) with placebo; no studies compared medications within classes against each other.¹

On individual symptom scores, intranasal steroids reduced sneezing, itching, congestion, and rhinorrhea more than placebo by more than 20%. Both intranasal steroids and oral antihistamines decreased itching and rhinorrhea a similar amount, but antihistamines reduced congestion by only 5% to 10% more than placebo.¹

This meta-analysis included only studies reporting TNSS as an outcome, and individual studies used varying TNSS scales. Investigators attributed heterogeneity in the studies to intraclass differences between medications.¹

Two drug company-sponsored RCTs (1616 patients combined, average age 30s, moderate to severe allergic rhinitis) published before the meta-analysis also demonstrated that the intranasal steroid fluticasone propionate modestly reduced TNSS compared with the oral antihistamine fexofenadine (1 point vs 1.3 on a scale of 0 to 12).² TABLE 1 summarizes the results of studies comparing intranasal steroids and oral antihistamines to reduce nasal symptoms.

TABLE 1
Intranasal steroids vs oral antihistamines for nasal symptom relief

Results for eye symptoms are mixed
A meta-analysis of 11 RCTs (1317 patients, average age 32) showed no significant difference in relief of eye symptoms between oral antihistamines (dexchlorpheniramine, terfenadine, and loratadine) and intranasal steroids (budesonide, beclomethasone, fluticasone, and triamcinolone) in patients with seasonal allergies, as measured by various symptom scores.³

Three other studies indicated that intranasal steroids (triamcinolone, fluticasone) relieved eye symptoms more effectively than oral antihistamines (loratadine, fexofenadine) based on mean reductions in TNSS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Total Ocular Symptom Score (TOSS).^4-6 Of these scoring systems, only the RQLQ has been clinically validated.⁷

One additional study (including 2 RCTs) showed conflicting results.² TABLE 2 summarizes the results of studies comparing intranasal steroids and oral antihistamines to relieve eye symptoms.

TABLE 2
How intranasal steroids compare with oral antihistamines for reducing eye symptoms

Antihistamines cost less than steroids and are available OTC
Oral antihistamines are less expensive than intranasal steroids and are available over the counter. The cost of antihistamines ranges from $5.70 to $21.99 for a month of treatment, whereas the cost of intranasal steroids for the same period varies from $60.99 to $149.99.⁸

In the studies reviewed here, the 2 interventions showed similar harms, including sore throat, epistaxis, and headache.^2,4-6

Recommendations

The American Academy of Allergy, Asthma and Immunology’s 2010 guidelines conclude that intranasal steroids are first-line treatment for allergic rhinitis. If the patient prefers, use oral antihistamines.⁹

The Joint Task Force on Practice Parameters for Allergy and Immunology also recommends intranasal steroids as the most effective medication class for treating allergic rhinitis; no drug within the class is preferable to another. Daily administration is more effective than administration as needed, although the latter is an option. For treating ocular symptoms, intranasal corticosteroids and oral antihistamines work equally well.¹⁰

Evidence summary

The most commonly measured outcomes in allergic rhinitis and conjunctivitis trials are symptom scales, which are neither standardized nor clinically validated. Almost all the studies discussed here calculated outcomes as a percentage change from baseline symptom scores but didn’t provide absolute values, so it isn’t clear whether statistical differences are clinically relevant.

Steroids provide more relief of nasal symptoms
A meta-analysis of 21 randomized placebo-controlled trials (total 2821 patients, average age mid-30s) that compared changes in TNSS with intranasal steroids and oral antihistamines among adults with seasonal allergic rhinitis found that steroids reduced TNSS more than antihistamines.¹ Most of the patients had had moderate to severe symptoms for several years.

Investigators calculated percent changes from baseline in mean TNSS, which typically included sneezing, itching, congestion, and rhinorrhea, each usually scored on a scale of 0 to 3.¹ Individual RCTs compared one of 3 intranasal steroids (fluticasone, triamcinolone, or budesonide) and one of 3 oral antihistamines (cetirizine, loratadine, or fexofenadine) with placebo; no studies compared medications within classes against each other.¹

On individual symptom scores, intranasal steroids reduced sneezing, itching, congestion, and rhinorrhea more than placebo by more than 20%. Both intranasal steroids and oral antihistamines decreased itching and rhinorrhea a similar amount, but antihistamines reduced congestion by only 5% to 10% more than placebo.¹

This meta-analysis included only studies reporting TNSS as an outcome, and individual studies used varying TNSS scales. Investigators attributed heterogeneity in the studies to intraclass differences between medications.¹

Two drug company-sponsored RCTs (1616 patients combined, average age 30s, moderate to severe allergic rhinitis) published before the meta-analysis also demonstrated that the intranasal steroid fluticasone propionate modestly reduced TNSS compared with the oral antihistamine fexofenadine (1 point vs 1.3 on a scale of 0 to 12).² TABLE 1 summarizes the results of studies comparing intranasal steroids and oral antihistamines to reduce nasal symptoms.

TABLE 1
Intranasal steroids vs oral antihistamines for nasal symptom relief

Results for eye symptoms are mixed
A meta-analysis of 11 RCTs (1317 patients, average age 32) showed no significant difference in relief of eye symptoms between oral antihistamines (dexchlorpheniramine, terfenadine, and loratadine) and intranasal steroids (budesonide, beclomethasone, fluticasone, and triamcinolone) in patients with seasonal allergies, as measured by various symptom scores.³

Three other studies indicated that intranasal steroids (triamcinolone, fluticasone) relieved eye symptoms more effectively than oral antihistamines (loratadine, fexofenadine) based on mean reductions in TNSS, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Total Ocular Symptom Score (TOSS).^4-6 Of these scoring systems, only the RQLQ has been clinically validated.⁷

One additional study (including 2 RCTs) showed conflicting results.² TABLE 2 summarizes the results of studies comparing intranasal steroids and oral antihistamines to relieve eye symptoms.

TABLE 2
How intranasal steroids compare with oral antihistamines for reducing eye symptoms

Antihistamines cost less than steroids and are available OTC
Oral antihistamines are less expensive than intranasal steroids and are available over the counter. The cost of antihistamines ranges from $5.70 to $21.99 for a month of treatment, whereas the cost of intranasal steroids for the same period varies from $60.99 to $149.99.⁸

In the studies reviewed here, the 2 interventions showed similar harms, including sore throat, epistaxis, and headache.^2,4-6

Recommendations

The American Academy of Allergy, Asthma and Immunology’s 2010 guidelines conclude that intranasal steroids are first-line treatment for allergic rhinitis. If the patient prefers, use oral antihistamines.⁹

The Joint Task Force on Practice Parameters for Allergy and Immunology also recommends intranasal steroids as the most effective medication class for treating allergic rhinitis; no drug within the class is preferable to another. Daily administration is more effective than administration as needed, although the latter is an option. For treating ocular symptoms, intranasal corticosteroids and oral antihistamines work equally well.¹⁰

Evidence summary

An RCT compared breast emptying every 6 hours with no treatment for inflammatory breast symptoms in 213 women with 339 inflamed breasts.¹ Investigators classified symptoms into 3 groups based on milk leukocyte counts (MLC) and cultures from expressed milk (MC): infectious mastitis (MLC >10⁶/mL, MC >10³ bacteria/mL; n=165 breasts), noninfectious mastitis (MLC >10⁶/mL, MC <10³ bacteria/mL; n=48 breasts), and milk stasis, or inspissated milk (MLC <10⁶/mL, MC <10³ bacteria/mL; n=126 breasts).

Breast emptying reduced the mean duration of symptoms in women with infectious mastitis (4.2 vs 6.7 days with no treatment; P<.001) and noninfectious mastitis (3.2 vs 7.9 days with no treatment; P<.001). However, it didn’t shorten mean symptom duration in women with milk stasis (2.1 vs 2.3 days with no treatment; P not significant).¹

Moreover, breast emptying allowed more women with infectious and noninfectious mastitis to return to normal lactation within 2 weeks. Rates of return to lactation for women with infectious mastitis were 51% with breast emptying compared with 15% with no treatment (number needed to treat [NNT]=2; 95% confidence interval [CI], 2-5). For women with noninfectious mastitis, the rates of return to lactation within 2 weeks were 96% with breast emptying compared with 21% with no treatment (NNT=1; 95% CI, 1-2).¹

Antibiotics plus breast emptying work better than emptying alone
The investigators further randomized a subgroup of women (165 involved breasts) with culture-positive mastitis into 3 treatment groups, each with 55 women: culture-directed antibiotics for 6 days plus breast emptying every 6 hours, breast emptying alone, and no treatment.

Antibiotics improved the rate of return to normal lactation over breast emptying alone (96% vs 51% normal lactation at 2 weeks; NNT=3; 95% CI, 2-3) and no treatment (96% vs 15% normal lactation at 2 weeks, NNT=1; 95% CI, 1-2). They also reduced the mean duration of symptoms (2.1 days with antibiotics vs 4.2 days with breast emptying alone and 6.7 days with no treatment; P<.001 for each).¹

Amoxicillin and cephradine produce similar results
A smaller RCT (N=25) compared oral amoxicillin with oral cephradine for women with a clinical diagnosis of mastitis based on oral temperature above 37.6°C, breast tenderness, and erythema.² Investigators prescribed 7 days of amoxicillin (500 mg every 8 h; n=13) or cephradine (500 mg every 6 h; n=12) and instructed women to continue breastfeeding and apply warm, moist compresses to the involved breast every 4 to 6 hours. They also performed milk cultures on all women. The cultures grew penicillin-resistant staphylococci (15 women; 7 treated with amoxicillin and 8 with cephradine) and penicillin-sensitive streptococci (6 women).

After 7 days, the investigators found no significant differences in fever, breast tenderness, or erythema between the 2 groups (relative risk=0.85; 95% CI, 0.65-1.12, favoring cephradine).^2,3 Two treatment failures occurred in the amoxicillin-treated group, both in women who had positive cultures for Staphylococcus aureus.²

A Cochrane systematic review of the 2 RCTs described here concluded that insufficient evidence exists to support or refute antibiotic therapy for treating lactational mastitis.³

Recommendations

The World Health Organization (WHO) recommends continued breastfeeding and improving breastfeeding technique for women with mastitis. WHO advises ensuring proper infant attachment, frequent breastfeeding, and expression of breast milk by hand or pump, if necessary. They urge clinicians to promote continued breastfeeding by providing encouragement and reassurance about its value.⁴

The Academy of Breastfeeding Medicine (ABM) recommends anti-inflammatory medications for analgesia to allow women with mastitis to continue to breastfeed. Hot packs or a hot shower also may alleviate symptoms.⁵

WHO and ABM both recommend prescribing a 14-day course of antibiotics effective against S aureus for women whose symptoms don’t improve after breast emptying for 12 to 24 hours.^4,5

Evidence summary

An RCT compared breast emptying every 6 hours with no treatment for inflammatory breast symptoms in 213 women with 339 inflamed breasts.¹ Investigators classified symptoms into 3 groups based on milk leukocyte counts (MLC) and cultures from expressed milk (MC): infectious mastitis (MLC >10⁶/mL, MC >10³ bacteria/mL; n=165 breasts), noninfectious mastitis (MLC >10⁶/mL, MC <10³ bacteria/mL; n=48 breasts), and milk stasis, or inspissated milk (MLC <10⁶/mL, MC <10³ bacteria/mL; n=126 breasts).

Breast emptying reduced the mean duration of symptoms in women with infectious mastitis (4.2 vs 6.7 days with no treatment; P<.001) and noninfectious mastitis (3.2 vs 7.9 days with no treatment; P<.001). However, it didn’t shorten mean symptom duration in women with milk stasis (2.1 vs 2.3 days with no treatment; P not significant).¹

Moreover, breast emptying allowed more women with infectious and noninfectious mastitis to return to normal lactation within 2 weeks. Rates of return to lactation for women with infectious mastitis were 51% with breast emptying compared with 15% with no treatment (number needed to treat [NNT]=2; 95% confidence interval [CI], 2-5). For women with noninfectious mastitis, the rates of return to lactation within 2 weeks were 96% with breast emptying compared with 21% with no treatment (NNT=1; 95% CI, 1-2).¹

Antibiotics plus breast emptying work better than emptying alone
The investigators further randomized a subgroup of women (165 involved breasts) with culture-positive mastitis into 3 treatment groups, each with 55 women: culture-directed antibiotics for 6 days plus breast emptying every 6 hours, breast emptying alone, and no treatment.

Antibiotics improved the rate of return to normal lactation over breast emptying alone (96% vs 51% normal lactation at 2 weeks; NNT=3; 95% CI, 2-3) and no treatment (96% vs 15% normal lactation at 2 weeks, NNT=1; 95% CI, 1-2). They also reduced the mean duration of symptoms (2.1 days with antibiotics vs 4.2 days with breast emptying alone and 6.7 days with no treatment; P<.001 for each).¹

Amoxicillin and cephradine produce similar results
A smaller RCT (N=25) compared oral amoxicillin with oral cephradine for women with a clinical diagnosis of mastitis based on oral temperature above 37.6°C, breast tenderness, and erythema.² Investigators prescribed 7 days of amoxicillin (500 mg every 8 h; n=13) or cephradine (500 mg every 6 h; n=12) and instructed women to continue breastfeeding and apply warm, moist compresses to the involved breast every 4 to 6 hours. They also performed milk cultures on all women. The cultures grew penicillin-resistant staphylococci (15 women; 7 treated with amoxicillin and 8 with cephradine) and penicillin-sensitive streptococci (6 women).

After 7 days, the investigators found no significant differences in fever, breast tenderness, or erythema between the 2 groups (relative risk=0.85; 95% CI, 0.65-1.12, favoring cephradine).^2,3 Two treatment failures occurred in the amoxicillin-treated group, both in women who had positive cultures for Staphylococcus aureus.²

A Cochrane systematic review of the 2 RCTs described here concluded that insufficient evidence exists to support or refute antibiotic therapy for treating lactational mastitis.³

Recommendations

The World Health Organization (WHO) recommends continued breastfeeding and improving breastfeeding technique for women with mastitis. WHO advises ensuring proper infant attachment, frequent breastfeeding, and expression of breast milk by hand or pump, if necessary. They urge clinicians to promote continued breastfeeding by providing encouragement and reassurance about its value.⁴

The Academy of Breastfeeding Medicine (ABM) recommends anti-inflammatory medications for analgesia to allow women with mastitis to continue to breastfeed. Hot packs or a hot shower also may alleviate symptoms.⁵

WHO and ABM both recommend prescribing a 14-day course of antibiotics effective against S aureus for women whose symptoms don’t improve after breast emptying for 12 to 24 hours.^4,5

Evidence summary

An RCT compared breast emptying every 6 hours with no treatment for inflammatory breast symptoms in 213 women with 339 inflamed breasts.¹ Investigators classified symptoms into 3 groups based on milk leukocyte counts (MLC) and cultures from expressed milk (MC): infectious mastitis (MLC >10⁶/mL, MC >10³ bacteria/mL; n=165 breasts), noninfectious mastitis (MLC >10⁶/mL, MC <10³ bacteria/mL; n=48 breasts), and milk stasis, or inspissated milk (MLC <10⁶/mL, MC <10³ bacteria/mL; n=126 breasts).

Breast emptying reduced the mean duration of symptoms in women with infectious mastitis (4.2 vs 6.7 days with no treatment; P<.001) and noninfectious mastitis (3.2 vs 7.9 days with no treatment; P<.001). However, it didn’t shorten mean symptom duration in women with milk stasis (2.1 vs 2.3 days with no treatment; P not significant).¹

Moreover, breast emptying allowed more women with infectious and noninfectious mastitis to return to normal lactation within 2 weeks. Rates of return to lactation for women with infectious mastitis were 51% with breast emptying compared with 15% with no treatment (number needed to treat [NNT]=2; 95% confidence interval [CI], 2-5). For women with noninfectious mastitis, the rates of return to lactation within 2 weeks were 96% with breast emptying compared with 21% with no treatment (NNT=1; 95% CI, 1-2).¹

Antibiotics plus breast emptying work better than emptying alone
The investigators further randomized a subgroup of women (165 involved breasts) with culture-positive mastitis into 3 treatment groups, each with 55 women: culture-directed antibiotics for 6 days plus breast emptying every 6 hours, breast emptying alone, and no treatment.

Antibiotics improved the rate of return to normal lactation over breast emptying alone (96% vs 51% normal lactation at 2 weeks; NNT=3; 95% CI, 2-3) and no treatment (96% vs 15% normal lactation at 2 weeks, NNT=1; 95% CI, 1-2). They also reduced the mean duration of symptoms (2.1 days with antibiotics vs 4.2 days with breast emptying alone and 6.7 days with no treatment; P<.001 for each).¹

Amoxicillin and cephradine produce similar results
A smaller RCT (N=25) compared oral amoxicillin with oral cephradine for women with a clinical diagnosis of mastitis based on oral temperature above 37.6°C, breast tenderness, and erythema.² Investigators prescribed 7 days of amoxicillin (500 mg every 8 h; n=13) or cephradine (500 mg every 6 h; n=12) and instructed women to continue breastfeeding and apply warm, moist compresses to the involved breast every 4 to 6 hours. They also performed milk cultures on all women. The cultures grew penicillin-resistant staphylococci (15 women; 7 treated with amoxicillin and 8 with cephradine) and penicillin-sensitive streptococci (6 women).

After 7 days, the investigators found no significant differences in fever, breast tenderness, or erythema between the 2 groups (relative risk=0.85; 95% CI, 0.65-1.12, favoring cephradine).^2,3 Two treatment failures occurred in the amoxicillin-treated group, both in women who had positive cultures for Staphylococcus aureus.²

A Cochrane systematic review of the 2 RCTs described here concluded that insufficient evidence exists to support or refute antibiotic therapy for treating lactational mastitis.³

Recommendations

The World Health Organization (WHO) recommends continued breastfeeding and improving breastfeeding technique for women with mastitis. WHO advises ensuring proper infant attachment, frequent breastfeeding, and expression of breast milk by hand or pump, if necessary. They urge clinicians to promote continued breastfeeding by providing encouragement and reassurance about its value.⁴

The Academy of Breastfeeding Medicine (ABM) recommends anti-inflammatory medications for analgesia to allow women with mastitis to continue to breastfeed. Hot packs or a hot shower also may alleviate symptoms.⁵

WHO and ABM both recommend prescribing a 14-day course of antibiotics effective against S aureus for women whose symptoms don’t improve after breast emptying for 12 to 24 hours.^4,5

Evidence summary

A prospective cohort study of 220 patients from an outpatient dermatology center in Amsterdam investigated the natural course of chronic urticaria and angioedema.¹ Researchers categorized patients according to subtypes: idiopathic urticaria-angioedema, idiopathic urticaria, idiopathic angioedema, physical and idiopathic urticaria, and physical urticaria only.

The duration of symptoms at enrollment wasn’t reported. Therapy wasn’t controlled and was composed of oral antihistamines, steroids, and other drugs.

One year after enrollment, 35% of patients had complete resolution of symptoms. Resolution rates ranged from a high of 59.6% in patients with idiopathic urticaria-angioedema to a low of 16.4% in patients who had urticaria with a physical cause.

A study finds 1-year control or improvement in chronic urticaria
Another prospective cohort study from an outpatient dermatology center in Brazil evaluated 125 patients with chronic urticaria-angioedema.² Participants were predominantly adults 20 to 40 years of age, with a mean duration of symptoms of 45 months.

Most patients had idiopathic disease (78%), but some had parasitic and skin infections, medication sensitivities, thyroid disease, and other problems that could contribute to skin hyperreactivity. Therapeutic interventions for underlying conditions or angioedema-urticaria weren’t controlled or reported.

One year after presentation, 58.4% of patients had symptoms “under control,” 31.7% were improved, and 8.9% were unchanged. One patient’s symptoms worsened.

Urticaria is less severe in patients older than 30 years
A prospective cohort study followed 62 patients with urticaria caused by cold from a tertiary referral center in Greece.³ The mean age at presentation was 42 years and the mean duration of symptoms was 10 years. The study followed patients for a mean of 9 years. Therapeutic interventions weren’t controlled or reported

Overall, 29% of patients experienced resolution of symptoms, 41.9% noted improvement, and 29% experienced worsening of symptoms. The mean time to resolution was 5.6 years. The study also found that chronic urticaria was less severe if patients developed the condition after 30 years of age.

Worst prognosis found in patients with cold-related urticaria
A retrospective cohort study identified 544 cases of chronic urticaria and angioedema in 22 years of records from a tertiary referral center in the Netherlands.⁴ The mean age at presentation was 35 years; patients had been symptomatic an average of 5 years. All patients were sent a questionnaire to fill out; 372 questionnaires were returned.

At 5 years after presentation, symptoms resolved in 29% of patients; at 10 years, the number of resolved cases increased to 44%. Patients with cold-related urticaria had the worst prognosis.

Zafirlukast has no effect
An RCT with a study group of 137 patients (mean age 41 years) compared the effectiveness of zafirlukast vs placebo for treating chronic urticaria symptoms. Zafirlukast showed no significant benefit over placebo; symptoms resolved or improved in 41.3% of all patients after 12 weeks.⁵

Recommendations

Habif’s Clinical Dermatology states that chronic urticaria:

• may last for months or years
• may be subject to lengthy and often un-rewarding evaluation
• resolves spontaneously in most cases.⁶

Evidence summary

A prospective cohort study of 220 patients from an outpatient dermatology center in Amsterdam investigated the natural course of chronic urticaria and angioedema.¹ Researchers categorized patients according to subtypes: idiopathic urticaria-angioedema, idiopathic urticaria, idiopathic angioedema, physical and idiopathic urticaria, and physical urticaria only.

The duration of symptoms at enrollment wasn’t reported. Therapy wasn’t controlled and was composed of oral antihistamines, steroids, and other drugs.

One year after enrollment, 35% of patients had complete resolution of symptoms. Resolution rates ranged from a high of 59.6% in patients with idiopathic urticaria-angioedema to a low of 16.4% in patients who had urticaria with a physical cause.

A study finds 1-year control or improvement in chronic urticaria
Another prospective cohort study from an outpatient dermatology center in Brazil evaluated 125 patients with chronic urticaria-angioedema.² Participants were predominantly adults 20 to 40 years of age, with a mean duration of symptoms of 45 months.

Most patients had idiopathic disease (78%), but some had parasitic and skin infections, medication sensitivities, thyroid disease, and other problems that could contribute to skin hyperreactivity. Therapeutic interventions for underlying conditions or angioedema-urticaria weren’t controlled or reported.

One year after presentation, 58.4% of patients had symptoms “under control,” 31.7% were improved, and 8.9% were unchanged. One patient’s symptoms worsened.

Urticaria is less severe in patients older than 30 years
A prospective cohort study followed 62 patients with urticaria caused by cold from a tertiary referral center in Greece.³ The mean age at presentation was 42 years and the mean duration of symptoms was 10 years. The study followed patients for a mean of 9 years. Therapeutic interventions weren’t controlled or reported

Overall, 29% of patients experienced resolution of symptoms, 41.9% noted improvement, and 29% experienced worsening of symptoms. The mean time to resolution was 5.6 years. The study also found that chronic urticaria was less severe if patients developed the condition after 30 years of age.

Worst prognosis found in patients with cold-related urticaria
A retrospective cohort study identified 544 cases of chronic urticaria and angioedema in 22 years of records from a tertiary referral center in the Netherlands.⁴ The mean age at presentation was 35 years; patients had been symptomatic an average of 5 years. All patients were sent a questionnaire to fill out; 372 questionnaires were returned.

At 5 years after presentation, symptoms resolved in 29% of patients; at 10 years, the number of resolved cases increased to 44%. Patients with cold-related urticaria had the worst prognosis.

Zafirlukast has no effect
An RCT with a study group of 137 patients (mean age 41 years) compared the effectiveness of zafirlukast vs placebo for treating chronic urticaria symptoms. Zafirlukast showed no significant benefit over placebo; symptoms resolved or improved in 41.3% of all patients after 12 weeks.⁵

Recommendations

Habif’s Clinical Dermatology states that chronic urticaria:

• may last for months or years
• may be subject to lengthy and often un-rewarding evaluation
• resolves spontaneously in most cases.⁶

Evidence summary

A prospective cohort study of 220 patients from an outpatient dermatology center in Amsterdam investigated the natural course of chronic urticaria and angioedema.¹ Researchers categorized patients according to subtypes: idiopathic urticaria-angioedema, idiopathic urticaria, idiopathic angioedema, physical and idiopathic urticaria, and physical urticaria only.

The duration of symptoms at enrollment wasn’t reported. Therapy wasn’t controlled and was composed of oral antihistamines, steroids, and other drugs.

One year after enrollment, 35% of patients had complete resolution of symptoms. Resolution rates ranged from a high of 59.6% in patients with idiopathic urticaria-angioedema to a low of 16.4% in patients who had urticaria with a physical cause.

A study finds 1-year control or improvement in chronic urticaria
Another prospective cohort study from an outpatient dermatology center in Brazil evaluated 125 patients with chronic urticaria-angioedema.² Participants were predominantly adults 20 to 40 years of age, with a mean duration of symptoms of 45 months.

Most patients had idiopathic disease (78%), but some had parasitic and skin infections, medication sensitivities, thyroid disease, and other problems that could contribute to skin hyperreactivity. Therapeutic interventions for underlying conditions or angioedema-urticaria weren’t controlled or reported.

One year after presentation, 58.4% of patients had symptoms “under control,” 31.7% were improved, and 8.9% were unchanged. One patient’s symptoms worsened.

Urticaria is less severe in patients older than 30 years
A prospective cohort study followed 62 patients with urticaria caused by cold from a tertiary referral center in Greece.³ The mean age at presentation was 42 years and the mean duration of symptoms was 10 years. The study followed patients for a mean of 9 years. Therapeutic interventions weren’t controlled or reported

Overall, 29% of patients experienced resolution of symptoms, 41.9% noted improvement, and 29% experienced worsening of symptoms. The mean time to resolution was 5.6 years. The study also found that chronic urticaria was less severe if patients developed the condition after 30 years of age.

Worst prognosis found in patients with cold-related urticaria
A retrospective cohort study identified 544 cases of chronic urticaria and angioedema in 22 years of records from a tertiary referral center in the Netherlands.⁴ The mean age at presentation was 35 years; patients had been symptomatic an average of 5 years. All patients were sent a questionnaire to fill out; 372 questionnaires were returned.

At 5 years after presentation, symptoms resolved in 29% of patients; at 10 years, the number of resolved cases increased to 44%. Patients with cold-related urticaria had the worst prognosis.

Zafirlukast has no effect
An RCT with a study group of 137 patients (mean age 41 years) compared the effectiveness of zafirlukast vs placebo for treating chronic urticaria symptoms. Zafirlukast showed no significant benefit over placebo; symptoms resolved or improved in 41.3% of all patients after 12 weeks.⁵

Recommendations

Habif’s Clinical Dermatology states that chronic urticaria:

• may last for months or years
• may be subject to lengthy and often un-rewarding evaluation
• resolves spontaneously in most cases.⁶

Evidence summary

No large trials with patient-oriented outcomes have evaluated cinnamon as a treatment for hyperlipidemia. One small RCT compared cinnamon with turmeric in 11 healthy individuals, ages 21 to 38 years, without diabetes or hyperlipidemia.

Investigators administered 3 g cinnamon or 2.8 g turmeric daily for 4 weeks; they found no significant change in fasting lipid values. Baseline lipid levels were 155 mg/dL for total cholesterol and 139 mg/dL for triglycerides. Clinical side effects of cinnamon included transient eructation (burping or reflux), headache, and a “burning stomach” sensation.¹

RCT with diabetes patients shows some positive results
Four small RCTs whose primary purpose was to investigate the effects of cinnamon supplements on blood glucose control in patients with diabetes also assessed blood lipid levels.

The first RCT studied 30 men and 30 women with type 2 diabetes, mean age 52 years. Patients had had diabetes (controlled with a sulfonylurea) for a mean of 7 years, but had no other medical conditions. Investigators randomized them into 6 groups of 10 subjects, each taking 1, 3, or 6 g of cinnamon or an equal number of placebo capsules daily for 40 days, followed by a 20-day washout period.

At 40 days, cinnamon at 3- and 6-g doses significantly reduced total cholesterol (12%-26% reduction; P<.05), low-density lipoprotein (LDL) (7%-27% reduction; P<.05), and triglycerides (23%-30% reduction; P<.05), but did not change high-density lipoprotein (HDL) levels. Cinnamon at the 1-g dose also reduced triglycerides and total cholesterol.² Investigators didn’t mention adverse effects.

Other studies find no change in lipids, but no harm either
However, 3 subsequent RCTs with a total of 181 patients found that cinnamon didn’t improve fasting lipid profiles in patients with type 2 diabetes.

In the first study, investigators randomized 25 postmenopausal women (mean age 63 years) with type 2 diabetes (controlled on any of 3 classes of oral medication) to receive either 1.5 g cinnamon or placebo daily for 6 weeks. Mean baseline lipid levels (total cholesterol=190 mg/dL; HDL=50 mg/dL; LDL=116 mg/dL; and triglycerides=113 mg/dL) did not change significantly. Investigators didn’t mention adverse effects.³

The second RCT, involving 79 patients (mean age 63 years) with type 2 diabetes on oral therapy, also found that 3 g cinnamon daily didn’t change lipid profiles over 4 months. Baseline lipid levels were: total cholesterol=209 mg/dL; HDL=56 mg/dL; LDL=135 mg/dL; and triglycerides=170 mg/dL. Investigators reported no adverse effects.⁴

The third RCT evaluated the effects of cinnamon supplementation compared with placebo on lipid levels and glycosylated hemoglobin (HbA1c) for 77 individuals with type 2 diabetes. Investigators recruited subjects of any age with diabetes controlled on a stable dose of oral agents and randomized them to receive either 500 mg cinnamon or placebo twice daily.

Subjects’ mean baseline cholesterol levels were: total cholesterol=170 mg/dL; HDL= 44 mg/dL; LDL=102 mg/dL; and triglycerides=132 mg/dL. There was no difference from baseline in fasting glucose, cholesterol levels (total, HDL, or LDL), or triglycerides at monthly intervals over 3 months, nor was there any change in HbA1c from baseline to 3 months.⁵

Recommendations

The American Diabetes Association states that cinnamon produces no benefit for people with diabetes.⁶ The Mayo Clinic states that there is little evidence that cinnamon reduces cholesterol levels, and does not recommend cinnamon as a treatment for high cholesterol.⁷

Evidence summary

No large trials with patient-oriented outcomes have evaluated cinnamon as a treatment for hyperlipidemia. One small RCT compared cinnamon with turmeric in 11 healthy individuals, ages 21 to 38 years, without diabetes or hyperlipidemia.

Investigators administered 3 g cinnamon or 2.8 g turmeric daily for 4 weeks; they found no significant change in fasting lipid values. Baseline lipid levels were 155 mg/dL for total cholesterol and 139 mg/dL for triglycerides. Clinical side effects of cinnamon included transient eructation (burping or reflux), headache, and a “burning stomach” sensation.¹

RCT with diabetes patients shows some positive results
Four small RCTs whose primary purpose was to investigate the effects of cinnamon supplements on blood glucose control in patients with diabetes also assessed blood lipid levels.

The first RCT studied 30 men and 30 women with type 2 diabetes, mean age 52 years. Patients had had diabetes (controlled with a sulfonylurea) for a mean of 7 years, but had no other medical conditions. Investigators randomized them into 6 groups of 10 subjects, each taking 1, 3, or 6 g of cinnamon or an equal number of placebo capsules daily for 40 days, followed by a 20-day washout period.

At 40 days, cinnamon at 3- and 6-g doses significantly reduced total cholesterol (12%-26% reduction; P<.05), low-density lipoprotein (LDL) (7%-27% reduction; P<.05), and triglycerides (23%-30% reduction; P<.05), but did not change high-density lipoprotein (HDL) levels. Cinnamon at the 1-g dose also reduced triglycerides and total cholesterol.² Investigators didn’t mention adverse effects.

Other studies find no change in lipids, but no harm either
However, 3 subsequent RCTs with a total of 181 patients found that cinnamon didn’t improve fasting lipid profiles in patients with type 2 diabetes.

In the first study, investigators randomized 25 postmenopausal women (mean age 63 years) with type 2 diabetes (controlled on any of 3 classes of oral medication) to receive either 1.5 g cinnamon or placebo daily for 6 weeks. Mean baseline lipid levels (total cholesterol=190 mg/dL; HDL=50 mg/dL; LDL=116 mg/dL; and triglycerides=113 mg/dL) did not change significantly. Investigators didn’t mention adverse effects.³

The second RCT, involving 79 patients (mean age 63 years) with type 2 diabetes on oral therapy, also found that 3 g cinnamon daily didn’t change lipid profiles over 4 months. Baseline lipid levels were: total cholesterol=209 mg/dL; HDL=56 mg/dL; LDL=135 mg/dL; and triglycerides=170 mg/dL. Investigators reported no adverse effects.⁴

The third RCT evaluated the effects of cinnamon supplementation compared with placebo on lipid levels and glycosylated hemoglobin (HbA1c) for 77 individuals with type 2 diabetes. Investigators recruited subjects of any age with diabetes controlled on a stable dose of oral agents and randomized them to receive either 500 mg cinnamon or placebo twice daily.

Subjects’ mean baseline cholesterol levels were: total cholesterol=170 mg/dL; HDL= 44 mg/dL; LDL=102 mg/dL; and triglycerides=132 mg/dL. There was no difference from baseline in fasting glucose, cholesterol levels (total, HDL, or LDL), or triglycerides at monthly intervals over 3 months, nor was there any change in HbA1c from baseline to 3 months.⁵

Recommendations

The American Diabetes Association states that cinnamon produces no benefit for people with diabetes.⁶ The Mayo Clinic states that there is little evidence that cinnamon reduces cholesterol levels, and does not recommend cinnamon as a treatment for high cholesterol.⁷

Evidence summary

No large trials with patient-oriented outcomes have evaluated cinnamon as a treatment for hyperlipidemia. One small RCT compared cinnamon with turmeric in 11 healthy individuals, ages 21 to 38 years, without diabetes or hyperlipidemia.

Investigators administered 3 g cinnamon or 2.8 g turmeric daily for 4 weeks; they found no significant change in fasting lipid values. Baseline lipid levels were 155 mg/dL for total cholesterol and 139 mg/dL for triglycerides. Clinical side effects of cinnamon included transient eructation (burping or reflux), headache, and a “burning stomach” sensation.¹

RCT with diabetes patients shows some positive results
Four small RCTs whose primary purpose was to investigate the effects of cinnamon supplements on blood glucose control in patients with diabetes also assessed blood lipid levels.

The first RCT studied 30 men and 30 women with type 2 diabetes, mean age 52 years. Patients had had diabetes (controlled with a sulfonylurea) for a mean of 7 years, but had no other medical conditions. Investigators randomized them into 6 groups of 10 subjects, each taking 1, 3, or 6 g of cinnamon or an equal number of placebo capsules daily for 40 days, followed by a 20-day washout period.

At 40 days, cinnamon at 3- and 6-g doses significantly reduced total cholesterol (12%-26% reduction; P<.05), low-density lipoprotein (LDL) (7%-27% reduction; P<.05), and triglycerides (23%-30% reduction; P<.05), but did not change high-density lipoprotein (HDL) levels. Cinnamon at the 1-g dose also reduced triglycerides and total cholesterol.² Investigators didn’t mention adverse effects.

Other studies find no change in lipids, but no harm either
However, 3 subsequent RCTs with a total of 181 patients found that cinnamon didn’t improve fasting lipid profiles in patients with type 2 diabetes.

In the first study, investigators randomized 25 postmenopausal women (mean age 63 years) with type 2 diabetes (controlled on any of 3 classes of oral medication) to receive either 1.5 g cinnamon or placebo daily for 6 weeks. Mean baseline lipid levels (total cholesterol=190 mg/dL; HDL=50 mg/dL; LDL=116 mg/dL; and triglycerides=113 mg/dL) did not change significantly. Investigators didn’t mention adverse effects.³

The second RCT, involving 79 patients (mean age 63 years) with type 2 diabetes on oral therapy, also found that 3 g cinnamon daily didn’t change lipid profiles over 4 months. Baseline lipid levels were: total cholesterol=209 mg/dL; HDL=56 mg/dL; LDL=135 mg/dL; and triglycerides=170 mg/dL. Investigators reported no adverse effects.⁴

The third RCT evaluated the effects of cinnamon supplementation compared with placebo on lipid levels and glycosylated hemoglobin (HbA1c) for 77 individuals with type 2 diabetes. Investigators recruited subjects of any age with diabetes controlled on a stable dose of oral agents and randomized them to receive either 500 mg cinnamon or placebo twice daily.

Subjects’ mean baseline cholesterol levels were: total cholesterol=170 mg/dL; HDL= 44 mg/dL; LDL=102 mg/dL; and triglycerides=132 mg/dL. There was no difference from baseline in fasting glucose, cholesterol levels (total, HDL, or LDL), or triglycerides at monthly intervals over 3 months, nor was there any change in HbA1c from baseline to 3 months.⁵

Recommendations

The American Diabetes Association states that cinnamon produces no benefit for people with diabetes.⁶ The Mayo Clinic states that there is little evidence that cinnamon reduces cholesterol levels, and does not recommend cinnamon as a treatment for high cholesterol.⁷

Evidence summary

Two prospective cohort studies evaluated the effect on glycemic control of a single glucocorticoid injection into the knee of patients with controlled type 2 diabetes (glycosylated hemoglobin A1c <7.0%). The first enrolled 9 patients with symptomatic osteoarthritis of the knee unresponsive to 3 months of nonsteroidal anti-inflammatory drugs (NSAIDs).¹ All received a 50-mg injection of methylprednisolone acetate after maximal aspiration of any joint fluid. No changes were made to the diabetes care regimen, including medication, diet, or exercise prescriptions.

With self-monitoring 6 times a day during the week after the injection, 7 patients showed an increase over baseline blood glucose levels of more than 2 standard deviations; values typically rose above 300 mg/dL. Peak blood sugar elevation occurred 5 to 84 hours after injection; the hyperglycemic effect lasted for 2 or 3 days.

In a second cohort study, 6 patients received a knee injection of 1 mL Celestone Chronodose (3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate, comparable in anti-inflammatory and glucocorticoid potency to 32 mg methylprednisolone acetate).² Patients monitored their blood glucose 6 times a day for 1 week; investigators measured fructosamine levels (a measure of intermediate-term glucose control) at baseline and again 2 weeks after injection.

The injection produced hyperglycemia in all participants, with peak blood glucose levels ranging from 251 to 430 mg/dL and time to peak glucose usually less than 6 hours. Fructosamine levels didn’t change significantly.

No change in glucose after a single shoulder injection
Two studies evaluated the effect of a single shoulder injection. One prospective cohort study included 18 patients with diabetes (type not specified, mean A1c=7.6%).³ All had shoulder pain unresponsive to NSAIDs for more than a month, had not changed diabetes medications within the preceding 2 weeks, and had not had steroid therapy within the preceding 3 months.

All patients received a single injection containing 35 mg methylprednisolone acetate into the anterior glenohumeral joint. They monitored their blood glucose levels 6 times a day for 1 week and had a fructosamine level drawn before injection and 2 weeks afterward. The injection produced no significant change in mean blood glucose or fructosamine levels.

But repeated shoulder injections raise postprandial glucose
In contrast, another prospective cohort study followed 11 patients (8 with diabetes) who received 3 injections of 3.75 mg cortivazol (comparable to 50 mg methylprednisolone acetate) at 3-day intervals into 1 shoulder joint.⁴ Investigators checked fasting and postprandial glucose levels before the first injection and on post-treatment days 1, 7, and 21.

The shoulder injections elevated post-prandial glucose levels (from 170±60 mg/dL at baseline to 258±100 mg/dL on day 1 and 252±87 mg/dL on day 7; P<.05 for both comparisons). Mean fasting glucose levels didn’t change, however.

Recommendations

The American Academy of Orthopedic Surgeons treatment guidelines for osteoarthritis of the knee don’t discuss possible adverse effects from steroid injections.⁵ The American Diabetes Association makes no recommendations regarding steroid injections in patients with diabetes.

Evidence summary

Two prospective cohort studies evaluated the effect on glycemic control of a single glucocorticoid injection into the knee of patients with controlled type 2 diabetes (glycosylated hemoglobin A1c <7.0%). The first enrolled 9 patients with symptomatic osteoarthritis of the knee unresponsive to 3 months of nonsteroidal anti-inflammatory drugs (NSAIDs).¹ All received a 50-mg injection of methylprednisolone acetate after maximal aspiration of any joint fluid. No changes were made to the diabetes care regimen, including medication, diet, or exercise prescriptions.

With self-monitoring 6 times a day during the week after the injection, 7 patients showed an increase over baseline blood glucose levels of more than 2 standard deviations; values typically rose above 300 mg/dL. Peak blood sugar elevation occurred 5 to 84 hours after injection; the hyperglycemic effect lasted for 2 or 3 days.

In a second cohort study, 6 patients received a knee injection of 1 mL Celestone Chronodose (3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate, comparable in anti-inflammatory and glucocorticoid potency to 32 mg methylprednisolone acetate).² Patients monitored their blood glucose 6 times a day for 1 week; investigators measured fructosamine levels (a measure of intermediate-term glucose control) at baseline and again 2 weeks after injection.

The injection produced hyperglycemia in all participants, with peak blood glucose levels ranging from 251 to 430 mg/dL and time to peak glucose usually less than 6 hours. Fructosamine levels didn’t change significantly.

No change in glucose after a single shoulder injection
Two studies evaluated the effect of a single shoulder injection. One prospective cohort study included 18 patients with diabetes (type not specified, mean A1c=7.6%).³ All had shoulder pain unresponsive to NSAIDs for more than a month, had not changed diabetes medications within the preceding 2 weeks, and had not had steroid therapy within the preceding 3 months.

All patients received a single injection containing 35 mg methylprednisolone acetate into the anterior glenohumeral joint. They monitored their blood glucose levels 6 times a day for 1 week and had a fructosamine level drawn before injection and 2 weeks afterward. The injection produced no significant change in mean blood glucose or fructosamine levels.

But repeated shoulder injections raise postprandial glucose
In contrast, another prospective cohort study followed 11 patients (8 with diabetes) who received 3 injections of 3.75 mg cortivazol (comparable to 50 mg methylprednisolone acetate) at 3-day intervals into 1 shoulder joint.⁴ Investigators checked fasting and postprandial glucose levels before the first injection and on post-treatment days 1, 7, and 21.

The shoulder injections elevated post-prandial glucose levels (from 170±60 mg/dL at baseline to 258±100 mg/dL on day 1 and 252±87 mg/dL on day 7; P<.05 for both comparisons). Mean fasting glucose levels didn’t change, however.

Recommendations

The American Academy of Orthopedic Surgeons treatment guidelines for osteoarthritis of the knee don’t discuss possible adverse effects from steroid injections.⁵ The American Diabetes Association makes no recommendations regarding steroid injections in patients with diabetes.

Evidence summary

Two prospective cohort studies evaluated the effect on glycemic control of a single glucocorticoid injection into the knee of patients with controlled type 2 diabetes (glycosylated hemoglobin A1c <7.0%). The first enrolled 9 patients with symptomatic osteoarthritis of the knee unresponsive to 3 months of nonsteroidal anti-inflammatory drugs (NSAIDs).¹ All received a 50-mg injection of methylprednisolone acetate after maximal aspiration of any joint fluid. No changes were made to the diabetes care regimen, including medication, diet, or exercise prescriptions.

With self-monitoring 6 times a day during the week after the injection, 7 patients showed an increase over baseline blood glucose levels of more than 2 standard deviations; values typically rose above 300 mg/dL. Peak blood sugar elevation occurred 5 to 84 hours after injection; the hyperglycemic effect lasted for 2 or 3 days.

In a second cohort study, 6 patients received a knee injection of 1 mL Celestone Chronodose (3 mg betamethasone acetate and 3 mg betamethasone sodium phosphate, comparable in anti-inflammatory and glucocorticoid potency to 32 mg methylprednisolone acetate).² Patients monitored their blood glucose 6 times a day for 1 week; investigators measured fructosamine levels (a measure of intermediate-term glucose control) at baseline and again 2 weeks after injection.

The injection produced hyperglycemia in all participants, with peak blood glucose levels ranging from 251 to 430 mg/dL and time to peak glucose usually less than 6 hours. Fructosamine levels didn’t change significantly.

No change in glucose after a single shoulder injection
Two studies evaluated the effect of a single shoulder injection. One prospective cohort study included 18 patients with diabetes (type not specified, mean A1c=7.6%).³ All had shoulder pain unresponsive to NSAIDs for more than a month, had not changed diabetes medications within the preceding 2 weeks, and had not had steroid therapy within the preceding 3 months.

All patients received a single injection containing 35 mg methylprednisolone acetate into the anterior glenohumeral joint. They monitored their blood glucose levels 6 times a day for 1 week and had a fructosamine level drawn before injection and 2 weeks afterward. The injection produced no significant change in mean blood glucose or fructosamine levels.

But repeated shoulder injections raise postprandial glucose
In contrast, another prospective cohort study followed 11 patients (8 with diabetes) who received 3 injections of 3.75 mg cortivazol (comparable to 50 mg methylprednisolone acetate) at 3-day intervals into 1 shoulder joint.⁴ Investigators checked fasting and postprandial glucose levels before the first injection and on post-treatment days 1, 7, and 21.

The shoulder injections elevated post-prandial glucose levels (from 170±60 mg/dL at baseline to 258±100 mg/dL on day 1 and 252±87 mg/dL on day 7; P<.05 for both comparisons). Mean fasting glucose levels didn’t change, however.

Recommendations

The American Academy of Orthopedic Surgeons treatment guidelines for osteoarthritis of the knee don’t discuss possible adverse effects from steroid injections.⁵ The American Diabetes Association makes no recommendations regarding steroid injections in patients with diabetes.

Evidence summary

A meta-analysis and 3 subsequent single-blinded RCTs showed a short-term decrease in blood pressure with daily consumption of chocolate. The meta-analysis was comprised of 5 randomized controlled parallel-group or crossover studies with a total of 173 adult patients, both normotensive and hypertensive. Patients ate dark chocolate, high-flavonol milk chocolate, white chocolate, or chocolate without flavonol daily for 14 to 15 days. Four studies used 100 to 105 g (approximately 3 oz) of chocolate (480 calories, 500 mg polyphenols, including flavonol), and 1 used 46 g (240 calories, 213 mg flavonol). Investigators didn’t report the percent of cocoa in the chocolate used.¹

Dark chocolate and high-flavonol milk chocolate significantly reduced both systolic blood pressure (–4.7 mm Hg; 95% confidence interval [CI], –7.6 to –1.8 mm Hg; P=.002) and diastolic pressure (–2.8 mm Hg; 95% CI, –4.8 to –0.8 mm Hg; P=.006). The study using the 46-g dose found no difference in blood pressure. Removing this outlier from the analysis didn’t alter the mean blood pressure changes.¹

From hypertensive to prehypertensive with help from chocolate
An RCT evaluated 44 adults, 56 to 73 years of age, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. Subjects consumed either 6.3 g (30 kcal) per day of dark chocolate (50% cocoa) or polyphenol-free (hence flavonol-free) white chocolate for 18 weeks.² Dark chocolate significantly reduced systolic and diastolic blood pressures (systolic: –2.9±1.6 mm Hg; P<.001; diastolic: –1.9±1.0 mm Hg; P<.001) compared with white chocolate.

Four patients who ate dark chocolate (18%) were reclassified from “hypertensive” to “prehypertensive.” None achieved lower-range prehypertension (<130/85) or optimal blood pressure, however. To place this finding in clinical perspective, the authors cite data from the Framingham Heart Study indicating that a 3-mm Hg reduction in systolic blood pressure should reduce the relative risk of stroke mortality by 8%, of mortality from coronary artery disease by 5%, and of all-cause mortality by 4%.²

More evidence of benefit of dark chocolate
A crossover RCT evaluated 19 hypertensive patients with glucose intolerance, but not overt diabetes, who ate either 100 g of flavonol-rich dark chocolate (50% cocoa) or 100 g of flavonol-free white chocolate for 15 days. Dark chocolate significantly reduced both 24-hour ambulatory systolic blood pressure (–4.52±3.94 mm Hg; P<.0001) and diastolic pressure (–4.17±3.29 mm Hg; P<.0001) compared with white chocolate. It also significantly decreased clinical blood pressure readings (systolic: –3.82±2.40 mm Hg; P<.0001; diastolic: –3.92±1.98 mm Hg; P<.0001).³

Another RCT evaluated blood pressure in 45 healthy adults given a 74-g dark chocolate bar (30% cocoa) or a 74-g placebo bar. Blood pressure decreased significantly 2 hours afterwards: –3.2±5.8 mm Hg systolic (P<.001) and –1.4±3.9 mm Hg diastolic (P<.001).⁴

Sugarless, but not sugared, cocoa shows effects on blood pressure
One week later, investigators compared 2 cups of cocoa (22 g cocoa powder) with 2 cups of sugarless cocoa and placebo. They found significant blood pressure reduction only with the sugarless drink. This study was the only one that reported sponsorship by a chocolate manufacturer.⁴

Long-term high-flavonoid consumption linked to lower heart disease mortality
A systematic review evaluated the long-term effects of a high-flavonoid diet over a period of 5 to 26 years. The review didn’t measure chocolate intake specifically, although the authors report that both milk and dark chocolate (percent cocoa not specified) are high in flavonoids, containing about 3 to 5 times as much as a comparable amount of black tea or red wine. Eleven prospective observational studies (N=190,000) met the criteria for this review.

Investigators compared occurrence and mortality rates for coronary heart disease and myocardial infarction among participants in the highest and lowest tertiles of flavonoid consumption. Participants in the highest tertile had significantly lower mortality from coronary heart disease than the lowest tertile, with a relative risk of 0.81 (95% CI, 0.71-0.92; no number needed to treat was available).⁵

Recommendations

We couldn’t find recommendations from major medical organizations. A Natural Medicines Comprehensive Database monograph states that consuming dark chocolate may modestly reduce blood pressure, but not enough evidence exists to rate chocolate’s effectiveness for cardiovascular disease, hypercholesterolemia, or isolated systolic hypertension.⁶

The US Food and Drug Administration warned one candy manufacturer against claiming that its chocolate-containing candy bars were “heart healthy,” noting that the candy bars also contained high levels of saturated fats.⁷

Evidence summary

A meta-analysis and 3 subsequent single-blinded RCTs showed a short-term decrease in blood pressure with daily consumption of chocolate. The meta-analysis was comprised of 5 randomized controlled parallel-group or crossover studies with a total of 173 adult patients, both normotensive and hypertensive. Patients ate dark chocolate, high-flavonol milk chocolate, white chocolate, or chocolate without flavonol daily for 14 to 15 days. Four studies used 100 to 105 g (approximately 3 oz) of chocolate (480 calories, 500 mg polyphenols, including flavonol), and 1 used 46 g (240 calories, 213 mg flavonol). Investigators didn’t report the percent of cocoa in the chocolate used.¹

Dark chocolate and high-flavonol milk chocolate significantly reduced both systolic blood pressure (–4.7 mm Hg; 95% confidence interval [CI], –7.6 to –1.8 mm Hg; P=.002) and diastolic pressure (–2.8 mm Hg; 95% CI, –4.8 to –0.8 mm Hg; P=.006). The study using the 46-g dose found no difference in blood pressure. Removing this outlier from the analysis didn’t alter the mean blood pressure changes.¹

From hypertensive to prehypertensive with help from chocolate
An RCT evaluated 44 adults, 56 to 73 years of age, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. Subjects consumed either 6.3 g (30 kcal) per day of dark chocolate (50% cocoa) or polyphenol-free (hence flavonol-free) white chocolate for 18 weeks.² Dark chocolate significantly reduced systolic and diastolic blood pressures (systolic: –2.9±1.6 mm Hg; P<.001; diastolic: –1.9±1.0 mm Hg; P<.001) compared with white chocolate.

Four patients who ate dark chocolate (18%) were reclassified from “hypertensive” to “prehypertensive.” None achieved lower-range prehypertension (<130/85) or optimal blood pressure, however. To place this finding in clinical perspective, the authors cite data from the Framingham Heart Study indicating that a 3-mm Hg reduction in systolic blood pressure should reduce the relative risk of stroke mortality by 8%, of mortality from coronary artery disease by 5%, and of all-cause mortality by 4%.²

More evidence of benefit of dark chocolate
A crossover RCT evaluated 19 hypertensive patients with glucose intolerance, but not overt diabetes, who ate either 100 g of flavonol-rich dark chocolate (50% cocoa) or 100 g of flavonol-free white chocolate for 15 days. Dark chocolate significantly reduced both 24-hour ambulatory systolic blood pressure (–4.52±3.94 mm Hg; P<.0001) and diastolic pressure (–4.17±3.29 mm Hg; P<.0001) compared with white chocolate. It also significantly decreased clinical blood pressure readings (systolic: –3.82±2.40 mm Hg; P<.0001; diastolic: –3.92±1.98 mm Hg; P<.0001).³

Another RCT evaluated blood pressure in 45 healthy adults given a 74-g dark chocolate bar (30% cocoa) or a 74-g placebo bar. Blood pressure decreased significantly 2 hours afterwards: –3.2±5.8 mm Hg systolic (P<.001) and –1.4±3.9 mm Hg diastolic (P<.001).⁴

Sugarless, but not sugared, cocoa shows effects on blood pressure
One week later, investigators compared 2 cups of cocoa (22 g cocoa powder) with 2 cups of sugarless cocoa and placebo. They found significant blood pressure reduction only with the sugarless drink. This study was the only one that reported sponsorship by a chocolate manufacturer.⁴

Long-term high-flavonoid consumption linked to lower heart disease mortality
A systematic review evaluated the long-term effects of a high-flavonoid diet over a period of 5 to 26 years. The review didn’t measure chocolate intake specifically, although the authors report that both milk and dark chocolate (percent cocoa not specified) are high in flavonoids, containing about 3 to 5 times as much as a comparable amount of black tea or red wine. Eleven prospective observational studies (N=190,000) met the criteria for this review.

Investigators compared occurrence and mortality rates for coronary heart disease and myocardial infarction among participants in the highest and lowest tertiles of flavonoid consumption. Participants in the highest tertile had significantly lower mortality from coronary heart disease than the lowest tertile, with a relative risk of 0.81 (95% CI, 0.71-0.92; no number needed to treat was available).⁵

Recommendations

We couldn’t find recommendations from major medical organizations. A Natural Medicines Comprehensive Database monograph states that consuming dark chocolate may modestly reduce blood pressure, but not enough evidence exists to rate chocolate’s effectiveness for cardiovascular disease, hypercholesterolemia, or isolated systolic hypertension.⁶

The US Food and Drug Administration warned one candy manufacturer against claiming that its chocolate-containing candy bars were “heart healthy,” noting that the candy bars also contained high levels of saturated fats.⁷

Evidence summary

A meta-analysis and 3 subsequent single-blinded RCTs showed a short-term decrease in blood pressure with daily consumption of chocolate. The meta-analysis was comprised of 5 randomized controlled parallel-group or crossover studies with a total of 173 adult patients, both normotensive and hypertensive. Patients ate dark chocolate, high-flavonol milk chocolate, white chocolate, or chocolate without flavonol daily for 14 to 15 days. Four studies used 100 to 105 g (approximately 3 oz) of chocolate (480 calories, 500 mg polyphenols, including flavonol), and 1 used 46 g (240 calories, 213 mg flavonol). Investigators didn’t report the percent of cocoa in the chocolate used.¹

Dark chocolate and high-flavonol milk chocolate significantly reduced both systolic blood pressure (–4.7 mm Hg; 95% confidence interval [CI], –7.6 to –1.8 mm Hg; P=.002) and diastolic pressure (–2.8 mm Hg; 95% CI, –4.8 to –0.8 mm Hg; P=.006). The study using the 46-g dose found no difference in blood pressure. Removing this outlier from the analysis didn’t alter the mean blood pressure changes.¹

From hypertensive to prehypertensive with help from chocolate
An RCT evaluated 44 adults, 56 to 73 years of age, with untreated upper-range prehypertension or stage 1 hypertension without concomitant risk factors. Subjects consumed either 6.3 g (30 kcal) per day of dark chocolate (50% cocoa) or polyphenol-free (hence flavonol-free) white chocolate for 18 weeks.² Dark chocolate significantly reduced systolic and diastolic blood pressures (systolic: –2.9±1.6 mm Hg; P<.001; diastolic: –1.9±1.0 mm Hg; P<.001) compared with white chocolate.

Four patients who ate dark chocolate (18%) were reclassified from “hypertensive” to “prehypertensive.” None achieved lower-range prehypertension (<130/85) or optimal blood pressure, however. To place this finding in clinical perspective, the authors cite data from the Framingham Heart Study indicating that a 3-mm Hg reduction in systolic blood pressure should reduce the relative risk of stroke mortality by 8%, of mortality from coronary artery disease by 5%, and of all-cause mortality by 4%.²

More evidence of benefit of dark chocolate
A crossover RCT evaluated 19 hypertensive patients with glucose intolerance, but not overt diabetes, who ate either 100 g of flavonol-rich dark chocolate (50% cocoa) or 100 g of flavonol-free white chocolate for 15 days. Dark chocolate significantly reduced both 24-hour ambulatory systolic blood pressure (–4.52±3.94 mm Hg; P<.0001) and diastolic pressure (–4.17±3.29 mm Hg; P<.0001) compared with white chocolate. It also significantly decreased clinical blood pressure readings (systolic: –3.82±2.40 mm Hg; P<.0001; diastolic: –3.92±1.98 mm Hg; P<.0001).³

Another RCT evaluated blood pressure in 45 healthy adults given a 74-g dark chocolate bar (30% cocoa) or a 74-g placebo bar. Blood pressure decreased significantly 2 hours afterwards: –3.2±5.8 mm Hg systolic (P<.001) and –1.4±3.9 mm Hg diastolic (P<.001).⁴

Sugarless, but not sugared, cocoa shows effects on blood pressure
One week later, investigators compared 2 cups of cocoa (22 g cocoa powder) with 2 cups of sugarless cocoa and placebo. They found significant blood pressure reduction only with the sugarless drink. This study was the only one that reported sponsorship by a chocolate manufacturer.⁴

Long-term high-flavonoid consumption linked to lower heart disease mortality
A systematic review evaluated the long-term effects of a high-flavonoid diet over a period of 5 to 26 years. The review didn’t measure chocolate intake specifically, although the authors report that both milk and dark chocolate (percent cocoa not specified) are high in flavonoids, containing about 3 to 5 times as much as a comparable amount of black tea or red wine. Eleven prospective observational studies (N=190,000) met the criteria for this review.

Investigators compared occurrence and mortality rates for coronary heart disease and myocardial infarction among participants in the highest and lowest tertiles of flavonoid consumption. Participants in the highest tertile had significantly lower mortality from coronary heart disease than the lowest tertile, with a relative risk of 0.81 (95% CI, 0.71-0.92; no number needed to treat was available).⁵

Recommendations

We couldn’t find recommendations from major medical organizations. A Natural Medicines Comprehensive Database monograph states that consuming dark chocolate may modestly reduce blood pressure, but not enough evidence exists to rate chocolate’s effectiveness for cardiovascular disease, hypercholesterolemia, or isolated systolic hypertension.⁶

The US Food and Drug Administration warned one candy manufacturer against claiming that its chocolate-containing candy bars were “heart healthy,” noting that the candy bars also contained high levels of saturated fats.⁷

Evidence summary

Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.¹ Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.

Decreases in mortality and hepatorenal syndrome

In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B₁₂ tablets) for 4 weeks.¹ The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”

Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.² Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).³

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).⁴

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.⁵ However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.⁶

Evidence summary

Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.¹ Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.

Decreases in mortality and hepatorenal syndrome

In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B₁₂ tablets) for 4 weeks.¹ The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”

Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.² Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).³

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).⁴

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.⁵ However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.⁶

Evidence summary

Patients with severe acute alcoholic hepatitis have elevated levels of serum tumor necrosis factor (TNF), suggesting that TNF release may play a role in liver inflammation.¹ Because pentoxifylline inhibits TNF synthesis, it has been evaluated as a potential therapy for alcoholic hepatitis.

Decreases in mortality and hepatorenal syndrome

In a hospital-based clinical trial, 101 patients admitted with severe alcoholic hepatitis (mean age 42 years, 74% men) were randomized to oral pentoxifylline 400 mg twice a day or placebo (vitamin B₁₂ tablets) for 4 weeks.¹ The main outcome measures were short-term survival and progression to hepatorenal syndrome. Severe alcoholic hepatitis was defined as a Maddrey discriminant factor (DF) >32, jaundice, and at least one of the following: tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit. The DF is calculated as follows: 4.6 × [prothrombin time in seconds – control time] + bilirubin (mg/dL). Medical management was “individualized according to each patient’s condition.”

Pentoxifylline therapy was associated with decreased mortality during the index hospitalization (relative risk [RR]=0.59; 95% confidence interval [CI], 0.35-0.97; number needed to treat [NNT]=5). Hepatorenal syndrome also decreased (RR=0.29; 95% CI, 0.13-0.65; NNT=4). Patients in the pentoxifylline group tended to have more headaches and gastrointestinal side effects, but no other serious health hazards were observed.

In a recently published abstract, 50 patients with severe alcoholic hepatitis (defined as DF >32) were enrolled in a randomized, double-blind, placebo-controlled trial of oral pentoxifylline, 400 mg twice a day or placebo for 4 weeks.² Short-term survival and changes in laboratory values (TNF, creatinine, and DF) were the primary outcome measures.

Survival was 76% in the pentoxifylline group compared with 60% in the placebo group (P not given). In the sub-group of patients who died, however, hepatorenal syndrome was the cause of death in 83% of the pentoxifylline group and 60% of the placebo group (P not given).

In a 1991 pilot study, also published only in abstract form, 22 patients admitted to the hospital with severe alcoholic hepatitis were randomized to receive oral pentoxifylline (1200 mg daily) or placebo for 10 days. Serum creatinine dropped 0.3 mg/dL in the treatment group and rose 2.1 mg/dL in the control group (P<.05). At 30 days, 3 patients in the control group had died compared with 1 in the treatment group (P=not significant).³

It’s not effective for patients who don’t respond to steroids

A cohort study evaluated the effect of switching to pentoxifylline in hospitalized patients with severe alcoholic hepatitis who didn’t respond to initial therapy with steroids. Researchers identified 121 patients who were treated initially with 40 mg oral prednisolone daily. The 36 patients who failed to show a drop in bilirubin levels within 7 days were switched to oral pentoxifylline, 400 mg twice a day.

In the pentoxifylline group, 69% of patients died within 2 months, 27.6% of whom had some form of renal insufficiency. This outcome wasn’t statistically different from that of 58 matched historical controls with severe alcoholic hepatitis who were maintained on oral prednisolone despite failure to respond within the first week of therapy (65% mortality, 20% with renal insufficiency).⁴

Recommendations

The American College of Gastroenterology doesn’t recommend giving pentoxifylline to patients with severe alcoholic hepatitis, citing lack of evidence for improvement of patient-oriented outcomes.⁵ However, a group of French hepatologists consider pentoxifylline a reasonable alternative to corticosteroids for severe acute alcoholic hepatitis based on the studies cited here.⁶

Evidence summary

A systematic review of 18 studies, including 3 RCTs, compared outcomes for expectant management (545 women) vs surgical evacuation (1408 women) for first-trimester spontaneous abortion.¹ A successful first-trimester spontaneous abortion was defined as vaginal bleeding for 3 weeks or less, fully expelled products of conception by 14 days, and no complications (infection, transfusion, uterine perforation, hospitalization, or death). Expectant management was successful in 93% overall, and 80% using only the data from RCTs.

An observational study evaluated 1096 consecutive patients with suspected first-trimester abortion, classified by ultrasound as complete, incomplete, missed, or anembryonic.² In the latter 3 categories, patients chose expectant management (478) or immediate surgical evacuation (208). Those choosing expectant management were monitored weekly and offered surgical evacuation if their abortion was incomplete after 1 month (TABLE). Complications arose in 6 of 451 patients (1%) managed expectantly for up to 46 days, and in 5 of 208 patients (2%) managed surgically (not statistically significant). One patient in the expectant group had emergency surgery and blood transfusion.²

A smaller observational study evaluated 108 women with first-trimester missed abortions or anembryonic pregnancies who chose either expectant (85 women) or surgical management. They were followed with weekly ultrasound (including color Doppler imaging) and serum β-hCG for up to 1 month. Fifty-three (62%) completed a spontaneous abortion at 14 days and 71 (84%) at 28 days. There were no significant differences in the rate of complications.³

A prospective trial compared psychological morbidity for 86 women with ultrasound-confirmed first-trimester missed abortions, randomized to expectant or surgical management. At 2 weeks, a self-administered questionnaire about the experience of pregnancy loss found no significant difference in psychological reactions. No increase was seen in anxiety or depression symptoms between women who had miscarried and healthy nonpregnant working women aged 19 to 39 years.⁴

Expert opinion recommends that women with spontaneous abortion beyond 13 weeks, a temperature >100.4° F, unstable blood pressure, uncontrolled vaginal bleeding, or evidence of endometritis or pelvic inflammatory disease should have surgical evacuation.²

TABLE
Completed abortions with expectant management by type²

Recommendations from others

UpToDate recommends expectant management for stable women who do not want any medical or surgical intervention, and are willing to wait for expulsion to occur. Surgical evacuation is recommended for women who are not stable because of bleeding or infection or for those who want immediate, definitive treatment of the nonviable pregnancy.⁵

Evidence summary

A systematic review of 18 studies, including 3 RCTs, compared outcomes for expectant management (545 women) vs surgical evacuation (1408 women) for first-trimester spontaneous abortion.¹ A successful first-trimester spontaneous abortion was defined as vaginal bleeding for 3 weeks or less, fully expelled products of conception by 14 days, and no complications (infection, transfusion, uterine perforation, hospitalization, or death). Expectant management was successful in 93% overall, and 80% using only the data from RCTs.

An observational study evaluated 1096 consecutive patients with suspected first-trimester abortion, classified by ultrasound as complete, incomplete, missed, or anembryonic.² In the latter 3 categories, patients chose expectant management (478) or immediate surgical evacuation (208). Those choosing expectant management were monitored weekly and offered surgical evacuation if their abortion was incomplete after 1 month (TABLE). Complications arose in 6 of 451 patients (1%) managed expectantly for up to 46 days, and in 5 of 208 patients (2%) managed surgically (not statistically significant). One patient in the expectant group had emergency surgery and blood transfusion.²

A smaller observational study evaluated 108 women with first-trimester missed abortions or anembryonic pregnancies who chose either expectant (85 women) or surgical management. They were followed with weekly ultrasound (including color Doppler imaging) and serum β-hCG for up to 1 month. Fifty-three (62%) completed a spontaneous abortion at 14 days and 71 (84%) at 28 days. There were no significant differences in the rate of complications.³

A prospective trial compared psychological morbidity for 86 women with ultrasound-confirmed first-trimester missed abortions, randomized to expectant or surgical management. At 2 weeks, a self-administered questionnaire about the experience of pregnancy loss found no significant difference in psychological reactions. No increase was seen in anxiety or depression symptoms between women who had miscarried and healthy nonpregnant working women aged 19 to 39 years.⁴

Expert opinion recommends that women with spontaneous abortion beyond 13 weeks, a temperature >100.4° F, unstable blood pressure, uncontrolled vaginal bleeding, or evidence of endometritis or pelvic inflammatory disease should have surgical evacuation.²

TABLE
Completed abortions with expectant management by type²

Recommendations from others

UpToDate recommends expectant management for stable women who do not want any medical or surgical intervention, and are willing to wait for expulsion to occur. Surgical evacuation is recommended for women who are not stable because of bleeding or infection or for those who want immediate, definitive treatment of the nonviable pregnancy.⁵

Evidence summary

A systematic review of 18 studies, including 3 RCTs, compared outcomes for expectant management (545 women) vs surgical evacuation (1408 women) for first-trimester spontaneous abortion.¹ A successful first-trimester spontaneous abortion was defined as vaginal bleeding for 3 weeks or less, fully expelled products of conception by 14 days, and no complications (infection, transfusion, uterine perforation, hospitalization, or death). Expectant management was successful in 93% overall, and 80% using only the data from RCTs.

An observational study evaluated 1096 consecutive patients with suspected first-trimester abortion, classified by ultrasound as complete, incomplete, missed, or anembryonic.² In the latter 3 categories, patients chose expectant management (478) or immediate surgical evacuation (208). Those choosing expectant management were monitored weekly and offered surgical evacuation if their abortion was incomplete after 1 month (TABLE). Complications arose in 6 of 451 patients (1%) managed expectantly for up to 46 days, and in 5 of 208 patients (2%) managed surgically (not statistically significant). One patient in the expectant group had emergency surgery and blood transfusion.²

A smaller observational study evaluated 108 women with first-trimester missed abortions or anembryonic pregnancies who chose either expectant (85 women) or surgical management. They were followed with weekly ultrasound (including color Doppler imaging) and serum β-hCG for up to 1 month. Fifty-three (62%) completed a spontaneous abortion at 14 days and 71 (84%) at 28 days. There were no significant differences in the rate of complications.³

A prospective trial compared psychological morbidity for 86 women with ultrasound-confirmed first-trimester missed abortions, randomized to expectant or surgical management. At 2 weeks, a self-administered questionnaire about the experience of pregnancy loss found no significant difference in psychological reactions. No increase was seen in anxiety or depression symptoms between women who had miscarried and healthy nonpregnant working women aged 19 to 39 years.⁴

Expert opinion recommends that women with spontaneous abortion beyond 13 weeks, a temperature >100.4° F, unstable blood pressure, uncontrolled vaginal bleeding, or evidence of endometritis or pelvic inflammatory disease should have surgical evacuation.²

TABLE
Completed abortions with expectant management by type²

Recommendations from others

UpToDate recommends expectant management for stable women who do not want any medical or surgical intervention, and are willing to wait for expulsion to occur. Surgical evacuation is recommended for women who are not stable because of bleeding or infection or for those who want immediate, definitive treatment of the nonviable pregnancy.⁵