The Journal of Family Practice

THE CASE

A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he’d had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103˚ F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid.

Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient’s physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest (FIGURE 1). Broad-spectrum antibiotics were initiated for presumed sepsis.

On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal.

By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus (HHV)-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies (ANAs) and anti-Smith (Sm) antibody titers.

A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face (FIGURE 2). Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.

THE DIAGNOSIS

We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function tests, and recent exposure to an offending drug. The patient did not have eosinophilia; however, atypical lymphocytes were present on his peripheral smear.

DISCUSSION

DRESS is typically characterized by fever, rash, eosinophilia, atypical lymphocytes, lymphadenopathy, and organ involvement (primarily liver, but multiple organ systems can be affected).¹ Patients with severe symptoms have renal involvement, anemia, respiratory and cardiac symptoms (chest pain, tachycardia, and myocarditis), and transaminase levels up to 5 times greater than normal.^1-3 Anticonvulsants and antibiotics are the most common offending classes among the medications that are associated with DRESS (TABLE 1).^2,4

The reported incidence of DRESS is between one in 1000 and one in 10,000 drug exposures.¹ Due to the broad presentation and a lack of established diagnostic criteria associated with DRESS, this number may be even higher. DRESS has a 10% mortality rate,¹ and hepatic necrosis is the most common cause of death.²

Certain people may be more prone to DRESS. People with certain gene mutations that code for drug detoxification enzymes have shown a greater incidence of DRESS.⁵ Viral reactivation, commonly of HHV-6, has also been shown to have an effect on the pathogenesis of DRESS. Additionally, genetic predisposition involving specific human leukocyte antigens (HLAs) makes certain people more prone to the development of DRESS (TABLE 2).^2,5

Case reports have demonstrated a link between certain autoimmune syndromes and DRESS, specifically Grave’s disease and type 1 diabetes mellitus.²

Patch testing and lymphocyte transformation tests can aid in the diagnosis of DRESS.

A unique finding of this case was the presence of elevated ANA and anti-Sm antibody titers at initial presentation, with spontaneous negative seroconversion 2 months later. Because of these 2 findings, as well as the patient’s leukopenia and rash, he briefly met 4 of the 11 criteria set forth by the American College of Rheumatology for a diagnosis of systemic lupus erythematosus (SLE).⁶ It is unclear whether the transiently elevated anti-Sm antibody titers were an acute phase reactant due to DRESS, a viral illness, or an evolving autoimmune process.

The false-positive rate for anti-Sm antibodies in association with DRESS has not been previously reported.

MAKING THE DIAGNOSIS

Distinguishing DRESS from other life-threatening cutaneous drug reactions, particularly Stevens-Johnson syndrome and toxic epidermal necrolysis, can be difficult. Likewise, acute bacterial/viral infections, autoimmune syndromes, vasculitis, and hematologic diseases can mimic DRESS.⁷ Exposure to an offending drug 2 to 6 weeks prior to the onset of symptoms is supportive of DRESS.

This scoring system can help. The RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) has developed a scoring system to aid in the accurate diagnosis of DRESS.^1,8 The scoring consists of 8 categories: fever, eosinophilia, enlarged lymph nodes, atypical lymphocytes, skin involvement, organ involvement, time of resolution, and the evaluation of other potential causes.¹ Each category is graded a number from -1 (not supportive of DRESS) to 2 (highly supportive of DRESS) based on the patient’s presentation. The total score grades potential cases as “no,” “possible,” “probable,” or “definite.”^1,8 In one review, cases classified as “probable” or “definite” by the RegiSCAR scoring system constituted 88% of the cases reported in the literature.¹

Two tests that can also aid in the diagnosis of DRESS include patch testing (exposing the skin to a diluted version of the suspected offending drug and observing for a local reaction) and lymphocyte transformation tests. The latter are a better method of diagnosing drug-induced DRESS, with a sensitivity of 60% to 70%, and a specificity of 85%.⁹ However, this testing is not readily available.

Long-term sequelae, such as Grave's disease and diabetes mellitus, have been reported following DRESS.

Once DRESS is diagnosed, the offending drug should be immediately discontinued. For mild cases, supportive treatment is recommended. For more severe cases, the use of corticosteroids tapered over several months is the treatment of choice.¹⁰ Further studies are needed to determine the optimal type of corticosteroids, as well as the dose, route, and duration of therapy. Immunotherapy, plasmapheresis, and antivirals have been used with mixed results.^10,11

Our patient was started on topical and systemic oral corticosteroids. Within 24 hours, his fever resolved and his rash improved. By HD 7, his laboratory values were normal and he was discharged.

The patient was advised that in the future, he should avoid exposure to the penicillin class of medication.

THE TAKEAWAY

The presence of rash, fever, lymphadenopathy, eosinophilia, atypical lymphocytes, liver involvement, and HHV-6 reactivation in the absence of sepsis should raise suspicion for DRESS. Early diagnosis, discontinuation of the culprit drug, and timely treatment are imperative in the management of the condition. Due to a potential genetic predisposition to DRESS, clinicians should use caution when treating first-degree family members with the same class of medication that was problematic for their relative. Long-term sequelae, such as Grave’s disease and diabetes mellitus, have been reported following DRESS. Therefore, long-term monitoring with appropriate testing is recommended.

THE CASE

A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he’d had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103˚ F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid.

Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient’s physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest (FIGURE 1). Broad-spectrum antibiotics were initiated for presumed sepsis.

On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal.

By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus (HHV)-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies (ANAs) and anti-Smith (Sm) antibody titers.

A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face (FIGURE 2). Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.

THE DIAGNOSIS

We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function tests, and recent exposure to an offending drug. The patient did not have eosinophilia; however, atypical lymphocytes were present on his peripheral smear.

DISCUSSION

DRESS is typically characterized by fever, rash, eosinophilia, atypical lymphocytes, lymphadenopathy, and organ involvement (primarily liver, but multiple organ systems can be affected).¹ Patients with severe symptoms have renal involvement, anemia, respiratory and cardiac symptoms (chest pain, tachycardia, and myocarditis), and transaminase levels up to 5 times greater than normal.^1-3 Anticonvulsants and antibiotics are the most common offending classes among the medications that are associated with DRESS (TABLE 1).^2,4

The reported incidence of DRESS is between one in 1000 and one in 10,000 drug exposures.¹ Due to the broad presentation and a lack of established diagnostic criteria associated with DRESS, this number may be even higher. DRESS has a 10% mortality rate,¹ and hepatic necrosis is the most common cause of death.²

Certain people may be more prone to DRESS. People with certain gene mutations that code for drug detoxification enzymes have shown a greater incidence of DRESS.⁵ Viral reactivation, commonly of HHV-6, has also been shown to have an effect on the pathogenesis of DRESS. Additionally, genetic predisposition involving specific human leukocyte antigens (HLAs) makes certain people more prone to the development of DRESS (TABLE 2).^2,5

Case reports have demonstrated a link between certain autoimmune syndromes and DRESS, specifically Grave’s disease and type 1 diabetes mellitus.²

Patch testing and lymphocyte transformation tests can aid in the diagnosis of DRESS.

A unique finding of this case was the presence of elevated ANA and anti-Sm antibody titers at initial presentation, with spontaneous negative seroconversion 2 months later. Because of these 2 findings, as well as the patient’s leukopenia and rash, he briefly met 4 of the 11 criteria set forth by the American College of Rheumatology for a diagnosis of systemic lupus erythematosus (SLE).⁶ It is unclear whether the transiently elevated anti-Sm antibody titers were an acute phase reactant due to DRESS, a viral illness, or an evolving autoimmune process.

The false-positive rate for anti-Sm antibodies in association with DRESS has not been previously reported.

MAKING THE DIAGNOSIS

Distinguishing DRESS from other life-threatening cutaneous drug reactions, particularly Stevens-Johnson syndrome and toxic epidermal necrolysis, can be difficult. Likewise, acute bacterial/viral infections, autoimmune syndromes, vasculitis, and hematologic diseases can mimic DRESS.⁷ Exposure to an offending drug 2 to 6 weeks prior to the onset of symptoms is supportive of DRESS.

This scoring system can help. The RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) has developed a scoring system to aid in the accurate diagnosis of DRESS.^1,8 The scoring consists of 8 categories: fever, eosinophilia, enlarged lymph nodes, atypical lymphocytes, skin involvement, organ involvement, time of resolution, and the evaluation of other potential causes.¹ Each category is graded a number from -1 (not supportive of DRESS) to 2 (highly supportive of DRESS) based on the patient’s presentation. The total score grades potential cases as “no,” “possible,” “probable,” or “definite.”^1,8 In one review, cases classified as “probable” or “definite” by the RegiSCAR scoring system constituted 88% of the cases reported in the literature.¹

Two tests that can also aid in the diagnosis of DRESS include patch testing (exposing the skin to a diluted version of the suspected offending drug and observing for a local reaction) and lymphocyte transformation tests. The latter are a better method of diagnosing drug-induced DRESS, with a sensitivity of 60% to 70%, and a specificity of 85%.⁹ However, this testing is not readily available.

Long-term sequelae, such as Grave's disease and diabetes mellitus, have been reported following DRESS.

Once DRESS is diagnosed, the offending drug should be immediately discontinued. For mild cases, supportive treatment is recommended. For more severe cases, the use of corticosteroids tapered over several months is the treatment of choice.¹⁰ Further studies are needed to determine the optimal type of corticosteroids, as well as the dose, route, and duration of therapy. Immunotherapy, plasmapheresis, and antivirals have been used with mixed results.^10,11

Our patient was started on topical and systemic oral corticosteroids. Within 24 hours, his fever resolved and his rash improved. By HD 7, his laboratory values were normal and he was discharged.

The patient was advised that in the future, he should avoid exposure to the penicillin class of medication.

THE TAKEAWAY

The presence of rash, fever, lymphadenopathy, eosinophilia, atypical lymphocytes, liver involvement, and HHV-6 reactivation in the absence of sepsis should raise suspicion for DRESS. Early diagnosis, discontinuation of the culprit drug, and timely treatment are imperative in the management of the condition. Due to a potential genetic predisposition to DRESS, clinicians should use caution when treating first-degree family members with the same class of medication that was problematic for their relative. Long-term sequelae, such as Grave’s disease and diabetes mellitus, have been reported following DRESS. Therefore, long-term monitoring with appropriate testing is recommended.

THE CASE

A 32-year-old man was admitted to our hospital with fever, chills, malaise, leukopenia, and a rash. About 3 weeks earlier, he’d had oral maxillofacial surgery and started a 10-day course of prophylactic amoxicillin/clavulanic acid. Fifteen days after the surgery, he developed a fever (temperature, 103˚ F), chills, arthralgia, myalgia, cough, diarrhea, and malaise. He was seen by his physician, who obtained a chest x-ray showing a lingular infiltrate. The physician diagnosed influenza and pneumonia in this patient, and prescribed oseltamivir, azithromycin, and an additional course of amoxicillin/clavulanic acid.

Upon admission to the hospital, laboratory tests revealed a white blood cell count (WBC) of 3.1 k/mcL (normal: 3.2-10.8 k/mcL). The patient’s physical examination was notable for lip edema, white mucous membrane plaques, submandibular and inguinal lymphadenopathy, and a morbilliform rash across his chest (FIGURE 1). Broad-spectrum antibiotics were initiated for presumed sepsis.

On hospital day (HD) 1, tests revealed a WBC count of 1.8 k/mcL, an erythrocyte sedimentation rate of 53 mm/hr (normal: 20-30 mm/hr for women, 15-20 mm/hr for men), and a C-reactive protein level of 6.7 mg/dL (normal: <0.5 mg/dL). A repeat chest x-ray and orofacial computerized tomography scan were normal.

By HD 3, all bacterial cultures were negative, but the patient was positive for human herpesvirus (HHV)-6 on viral cultures. His leukopenia persisted and he had elevated levels of alanine transaminase ranging from 40 to 73 U/L (normal: 6-43 U/L) and aspartate aminotransferase ranging from 66 to 108 U/L (normal range: 10-40 U/L), both downtrending during his hospitalization. He also had elevated levels of antinuclear antibodies (ANAs) and anti-Smith (Sm) antibody titers.

A posterior-auricular biopsy was consistent with lymphocytic perivasculitis. The rash continued to progress, involving his chest, abdomen, and face (FIGURE 2). Bacterial and viral cultures remained negative and on HD 4, broad-spectrum antibiotics were discontinued.

THE DIAGNOSIS

We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function tests, and recent exposure to an offending drug. The patient did not have eosinophilia; however, atypical lymphocytes were present on his peripheral smear.

DISCUSSION

DRESS is typically characterized by fever, rash, eosinophilia, atypical lymphocytes, lymphadenopathy, and organ involvement (primarily liver, but multiple organ systems can be affected).¹ Patients with severe symptoms have renal involvement, anemia, respiratory and cardiac symptoms (chest pain, tachycardia, and myocarditis), and transaminase levels up to 5 times greater than normal.^1-3 Anticonvulsants and antibiotics are the most common offending classes among the medications that are associated with DRESS (TABLE 1).^2,4

The reported incidence of DRESS is between one in 1000 and one in 10,000 drug exposures.¹ Due to the broad presentation and a lack of established diagnostic criteria associated with DRESS, this number may be even higher. DRESS has a 10% mortality rate,¹ and hepatic necrosis is the most common cause of death.²

Certain people may be more prone to DRESS. People with certain gene mutations that code for drug detoxification enzymes have shown a greater incidence of DRESS.⁵ Viral reactivation, commonly of HHV-6, has also been shown to have an effect on the pathogenesis of DRESS. Additionally, genetic predisposition involving specific human leukocyte antigens (HLAs) makes certain people more prone to the development of DRESS (TABLE 2).^2,5

Case reports have demonstrated a link between certain autoimmune syndromes and DRESS, specifically Grave’s disease and type 1 diabetes mellitus.²

Patch testing and lymphocyte transformation tests can aid in the diagnosis of DRESS.

A unique finding of this case was the presence of elevated ANA and anti-Sm antibody titers at initial presentation, with spontaneous negative seroconversion 2 months later. Because of these 2 findings, as well as the patient’s leukopenia and rash, he briefly met 4 of the 11 criteria set forth by the American College of Rheumatology for a diagnosis of systemic lupus erythematosus (SLE).⁶ It is unclear whether the transiently elevated anti-Sm antibody titers were an acute phase reactant due to DRESS, a viral illness, or an evolving autoimmune process.

The false-positive rate for anti-Sm antibodies in association with DRESS has not been previously reported.

MAKING THE DIAGNOSIS

Distinguishing DRESS from other life-threatening cutaneous drug reactions, particularly Stevens-Johnson syndrome and toxic epidermal necrolysis, can be difficult. Likewise, acute bacterial/viral infections, autoimmune syndromes, vasculitis, and hematologic diseases can mimic DRESS.⁷ Exposure to an offending drug 2 to 6 weeks prior to the onset of symptoms is supportive of DRESS.

This scoring system can help. The RegiSCAR (Registry of Severe Cutaneous Adverse Reaction) has developed a scoring system to aid in the accurate diagnosis of DRESS.^1,8 The scoring consists of 8 categories: fever, eosinophilia, enlarged lymph nodes, atypical lymphocytes, skin involvement, organ involvement, time of resolution, and the evaluation of other potential causes.¹ Each category is graded a number from -1 (not supportive of DRESS) to 2 (highly supportive of DRESS) based on the patient’s presentation. The total score grades potential cases as “no,” “possible,” “probable,” or “definite.”^1,8 In one review, cases classified as “probable” or “definite” by the RegiSCAR scoring system constituted 88% of the cases reported in the literature.¹

Two tests that can also aid in the diagnosis of DRESS include patch testing (exposing the skin to a diluted version of the suspected offending drug and observing for a local reaction) and lymphocyte transformation tests. The latter are a better method of diagnosing drug-induced DRESS, with a sensitivity of 60% to 70%, and a specificity of 85%.⁹ However, this testing is not readily available.

Long-term sequelae, such as Grave's disease and diabetes mellitus, have been reported following DRESS.

Once DRESS is diagnosed, the offending drug should be immediately discontinued. For mild cases, supportive treatment is recommended. For more severe cases, the use of corticosteroids tapered over several months is the treatment of choice.¹⁰ Further studies are needed to determine the optimal type of corticosteroids, as well as the dose, route, and duration of therapy. Immunotherapy, plasmapheresis, and antivirals have been used with mixed results.^10,11

Our patient was started on topical and systemic oral corticosteroids. Within 24 hours, his fever resolved and his rash improved. By HD 7, his laboratory values were normal and he was discharged.

The patient was advised that in the future, he should avoid exposure to the penicillin class of medication.

THE TAKEAWAY

The presence of rash, fever, lymphadenopathy, eosinophilia, atypical lymphocytes, liver involvement, and HHV-6 reactivation in the absence of sepsis should raise suspicion for DRESS. Early diagnosis, discontinuation of the culprit drug, and timely treatment are imperative in the management of the condition. Due to a potential genetic predisposition to DRESS, clinicians should use caution when treating first-degree family members with the same class of medication that was problematic for their relative. Long-term sequelae, such as Grave’s disease and diabetes mellitus, have been reported following DRESS. Therefore, long-term monitoring with appropriate testing is recommended.

EVIDENCE SUMMARY

A systematic review of 22 trials (13 case series, 8 prospective, nonrandomized studies, and one randomized controlled trial; 12,407 patients) conducted in Europe, Asia, and the Americas evaluated the likelihood of pregnancy with repeated use of precoital and postcoital hormonal contraception.¹ Some trials used more than one dose or medication. Many had inadequate reporting of research methods. Results were reported using the Pearl Index (PI)—the number of pregnancies per 100 woman-years.

In 11 studies (2700 patients), women took 750 mcg of levonorgestrel from 24 hours before to 24 hours after intercourse for an average duration of 5 cycles or months. Coital frequency varied from 1 to 15 times per month. The PI ranged from 0 to 18.6, with a pooled PI of 5.4 (95% confidence interval [CI], 4.1-7.0). Three of the trials (915 patients), with research methods reported as good, had a pooled PI of 8.9 (95% CI, 5.1-14.4). No serious adverse effects were reported in 10 of the 11 studies, but menstrual irregularity was commonly observed. In one of the largest studies (1315 patients), only 3% of women discontinued treatment because of adverse effects.

Six other trials (5785 patients) of levonorgestrel taken at doses ranging from 150 mcg to 1 mg for a mean duration of 9.2 cycles reported PIs of 0 to 9. Breakthrough bleeding was the most common adverse event. When all 17 studies of levonorgestrel were combined, the PI was 4.9 (95% CI, 4.3-5.5). The remaining studies in the systematic review described medicines not commonly used for emergency contraception or not available in the United States.

Other reported adverse effects: Headache, nausea, abdominal pain

A prospective, open-label study enrolled 321 women 18 to 45 years of age from Asia, Europe, and South America to evaluate the safety and efficacy of levonorgestrel 1.5 mg taken before or within 24 hours of intercourse as the exclusive means of contraception.² Women who were lactating or recently postpartum were excluded; condoms were permitted for women who had concerns about risk of sexually transmitted illness. Data analysis included estimates of perfect use (consistent and correct use of levonorgestrel only) and typical use (use of other contraceptive methods in addition to levonorgestrel).

At baseline, weight, blood pressure, and hemoglobin were documented, and follow-up visits occurred at 2.5, 4.5, and 6.5 months. Pregnancy tests, blood pressure, and adverse effects were assessed at each visit; weight and hemoglobin were evaluated at the final visit. The primary outcome measure was the PI in women younger than 35 years who used only levonorgestrel for contraception.

In women younger than 35 years (208 patients), the PI was 11 (95% CI, 5.7-13.1) with perfect use and 10.3 (95% CI, 5.4-19.9) with typical use. In all ages 18 to 45 years, the PI was 7.1 (95% CI, 3.8-13.1) for typical use and 7.5 (95% CI, 4-13.9) for perfect use. Most women took 4 to 6 doses per month.

The most commonly reported adverse effects were headache (29%), nausea or abdominal pain (16%), influenza (11%), and acne or candidiasis (8%). Bleeding patterns varied with a tendency toward longer bleeding initially and lighter menstrual periods and less anemia in some patients at the end of the study.

RECOMMENDATIONS

The Office of Population Research at Princeton University suggests that moderate repeat use of emergency contraceptives is unlikely to cause serious harm, but estimates that women using progestin-only emergency contraception on a regular basis would have a 20% chance of pregnancy in a year.³

The American College of Obstetricians and Gynecologists states that long-term use of emergency contraception is less effective than other methods and may result in higher hormone levels and more adverse effects than other established means.⁴

The International Consortium for Emergency Contraception concluded that there is no basis for limiting the number of times that emergency contraceptives may be used in a menstrual cycle, that emergency contraceptives are safe, and that, although they are less effective than other forms of long-term contraception, using them repeatedly is more effective than using no method.⁵

The Society of Obstetricians and Gynecologists of Canada states that emergency contraception is intended for occasional use as a backup method.⁶ The Society also notes that repeat use isn’t as effective as regular use of other forms of contraception.

Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%.

The Faculty of Sexual & Reproductive Healthcare of the (British) Royal College of Obstetricians and Gynaecologists says that use of levonorgestrel can be considered even if previously used one or more times in a menstrual cycle (SOR: D, based on non-analytical studies and expert opinion).⁷ The organization also recommends that emergency contraceptive providers share with patients that oral emergency contraceptive methods should not be used for long-term contraception (SOR: Good Practice Point, based on clinical experience of the guideline development group).

The Guttmacher Institute reports that without contraception, approximately 85% of sexually active women become pregnant each year.⁸ Long-acting reversible methods, such as implants and intrauterine devices, have annual pregnancy rates of 0.05% to 0.8%. With perfect (consistent and correct) use, combined oral contraceptives have a 0.3% annual pregnancy rate, but the rate rises to 9% with typical use. Condoms, when used perfectly, are associated with a 2% annual rate of pregnancy compared with an 18% rate with typical use.

EVIDENCE SUMMARY

A systematic review of 22 trials (13 case series, 8 prospective, nonrandomized studies, and one randomized controlled trial; 12,407 patients) conducted in Europe, Asia, and the Americas evaluated the likelihood of pregnancy with repeated use of precoital and postcoital hormonal contraception.¹ Some trials used more than one dose or medication. Many had inadequate reporting of research methods. Results were reported using the Pearl Index (PI)—the number of pregnancies per 100 woman-years.

In 11 studies (2700 patients), women took 750 mcg of levonorgestrel from 24 hours before to 24 hours after intercourse for an average duration of 5 cycles or months. Coital frequency varied from 1 to 15 times per month. The PI ranged from 0 to 18.6, with a pooled PI of 5.4 (95% confidence interval [CI], 4.1-7.0). Three of the trials (915 patients), with research methods reported as good, had a pooled PI of 8.9 (95% CI, 5.1-14.4). No serious adverse effects were reported in 10 of the 11 studies, but menstrual irregularity was commonly observed. In one of the largest studies (1315 patients), only 3% of women discontinued treatment because of adverse effects.

Six other trials (5785 patients) of levonorgestrel taken at doses ranging from 150 mcg to 1 mg for a mean duration of 9.2 cycles reported PIs of 0 to 9. Breakthrough bleeding was the most common adverse event. When all 17 studies of levonorgestrel were combined, the PI was 4.9 (95% CI, 4.3-5.5). The remaining studies in the systematic review described medicines not commonly used for emergency contraception or not available in the United States.

Other reported adverse effects: Headache, nausea, abdominal pain

A prospective, open-label study enrolled 321 women 18 to 45 years of age from Asia, Europe, and South America to evaluate the safety and efficacy of levonorgestrel 1.5 mg taken before or within 24 hours of intercourse as the exclusive means of contraception.² Women who were lactating or recently postpartum were excluded; condoms were permitted for women who had concerns about risk of sexually transmitted illness. Data analysis included estimates of perfect use (consistent and correct use of levonorgestrel only) and typical use (use of other contraceptive methods in addition to levonorgestrel).

At baseline, weight, blood pressure, and hemoglobin were documented, and follow-up visits occurred at 2.5, 4.5, and 6.5 months. Pregnancy tests, blood pressure, and adverse effects were assessed at each visit; weight and hemoglobin were evaluated at the final visit. The primary outcome measure was the PI in women younger than 35 years who used only levonorgestrel for contraception.

In women younger than 35 years (208 patients), the PI was 11 (95% CI, 5.7-13.1) with perfect use and 10.3 (95% CI, 5.4-19.9) with typical use. In all ages 18 to 45 years, the PI was 7.1 (95% CI, 3.8-13.1) for typical use and 7.5 (95% CI, 4-13.9) for perfect use. Most women took 4 to 6 doses per month.

The most commonly reported adverse effects were headache (29%), nausea or abdominal pain (16%), influenza (11%), and acne or candidiasis (8%). Bleeding patterns varied with a tendency toward longer bleeding initially and lighter menstrual periods and less anemia in some patients at the end of the study.

RECOMMENDATIONS

The Office of Population Research at Princeton University suggests that moderate repeat use of emergency contraceptives is unlikely to cause serious harm, but estimates that women using progestin-only emergency contraception on a regular basis would have a 20% chance of pregnancy in a year.³

The American College of Obstetricians and Gynecologists states that long-term use of emergency contraception is less effective than other methods and may result in higher hormone levels and more adverse effects than other established means.⁴

The International Consortium for Emergency Contraception concluded that there is no basis for limiting the number of times that emergency contraceptives may be used in a menstrual cycle, that emergency contraceptives are safe, and that, although they are less effective than other forms of long-term contraception, using them repeatedly is more effective than using no method.⁵

The Society of Obstetricians and Gynecologists of Canada states that emergency contraception is intended for occasional use as a backup method.⁶ The Society also notes that repeat use isn’t as effective as regular use of other forms of contraception.

Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%.

The Faculty of Sexual & Reproductive Healthcare of the (British) Royal College of Obstetricians and Gynaecologists says that use of levonorgestrel can be considered even if previously used one or more times in a menstrual cycle (SOR: D, based on non-analytical studies and expert opinion).⁷ The organization also recommends that emergency contraceptive providers share with patients that oral emergency contraceptive methods should not be used for long-term contraception (SOR: Good Practice Point, based on clinical experience of the guideline development group).

The Guttmacher Institute reports that without contraception, approximately 85% of sexually active women become pregnant each year.⁸ Long-acting reversible methods, such as implants and intrauterine devices, have annual pregnancy rates of 0.05% to 0.8%. With perfect (consistent and correct) use, combined oral contraceptives have a 0.3% annual pregnancy rate, but the rate rises to 9% with typical use. Condoms, when used perfectly, are associated with a 2% annual rate of pregnancy compared with an 18% rate with typical use.

EVIDENCE SUMMARY

A systematic review of 22 trials (13 case series, 8 prospective, nonrandomized studies, and one randomized controlled trial; 12,407 patients) conducted in Europe, Asia, and the Americas evaluated the likelihood of pregnancy with repeated use of precoital and postcoital hormonal contraception.¹ Some trials used more than one dose or medication. Many had inadequate reporting of research methods. Results were reported using the Pearl Index (PI)—the number of pregnancies per 100 woman-years.

In 11 studies (2700 patients), women took 750 mcg of levonorgestrel from 24 hours before to 24 hours after intercourse for an average duration of 5 cycles or months. Coital frequency varied from 1 to 15 times per month. The PI ranged from 0 to 18.6, with a pooled PI of 5.4 (95% confidence interval [CI], 4.1-7.0). Three of the trials (915 patients), with research methods reported as good, had a pooled PI of 8.9 (95% CI, 5.1-14.4). No serious adverse effects were reported in 10 of the 11 studies, but menstrual irregularity was commonly observed. In one of the largest studies (1315 patients), only 3% of women discontinued treatment because of adverse effects.

Six other trials (5785 patients) of levonorgestrel taken at doses ranging from 150 mcg to 1 mg for a mean duration of 9.2 cycles reported PIs of 0 to 9. Breakthrough bleeding was the most common adverse event. When all 17 studies of levonorgestrel were combined, the PI was 4.9 (95% CI, 4.3-5.5). The remaining studies in the systematic review described medicines not commonly used for emergency contraception or not available in the United States.

Other reported adverse effects: Headache, nausea, abdominal pain

A prospective, open-label study enrolled 321 women 18 to 45 years of age from Asia, Europe, and South America to evaluate the safety and efficacy of levonorgestrel 1.5 mg taken before or within 24 hours of intercourse as the exclusive means of contraception.² Women who were lactating or recently postpartum were excluded; condoms were permitted for women who had concerns about risk of sexually transmitted illness. Data analysis included estimates of perfect use (consistent and correct use of levonorgestrel only) and typical use (use of other contraceptive methods in addition to levonorgestrel).

At baseline, weight, blood pressure, and hemoglobin were documented, and follow-up visits occurred at 2.5, 4.5, and 6.5 months. Pregnancy tests, blood pressure, and adverse effects were assessed at each visit; weight and hemoglobin were evaluated at the final visit. The primary outcome measure was the PI in women younger than 35 years who used only levonorgestrel for contraception.

In women younger than 35 years (208 patients), the PI was 11 (95% CI, 5.7-13.1) with perfect use and 10.3 (95% CI, 5.4-19.9) with typical use. In all ages 18 to 45 years, the PI was 7.1 (95% CI, 3.8-13.1) for typical use and 7.5 (95% CI, 4-13.9) for perfect use. Most women took 4 to 6 doses per month.

The most commonly reported adverse effects were headache (29%), nausea or abdominal pain (16%), influenza (11%), and acne or candidiasis (8%). Bleeding patterns varied with a tendency toward longer bleeding initially and lighter menstrual periods and less anemia in some patients at the end of the study.

RECOMMENDATIONS

The Office of Population Research at Princeton University suggests that moderate repeat use of emergency contraceptives is unlikely to cause serious harm, but estimates that women using progestin-only emergency contraception on a regular basis would have a 20% chance of pregnancy in a year.³

The American College of Obstetricians and Gynecologists states that long-term use of emergency contraception is less effective than other methods and may result in higher hormone levels and more adverse effects than other established means.⁴

The International Consortium for Emergency Contraception concluded that there is no basis for limiting the number of times that emergency contraceptives may be used in a menstrual cycle, that emergency contraceptives are safe, and that, although they are less effective than other forms of long-term contraception, using them repeatedly is more effective than using no method.⁵

The Society of Obstetricians and Gynecologists of Canada states that emergency contraception is intended for occasional use as a backup method.⁶ The Society also notes that repeat use isn’t as effective as regular use of other forms of contraception.

Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%.

The Faculty of Sexual & Reproductive Healthcare of the (British) Royal College of Obstetricians and Gynaecologists says that use of levonorgestrel can be considered even if previously used one or more times in a menstrual cycle (SOR: D, based on non-analytical studies and expert opinion).⁷ The organization also recommends that emergency contraceptive providers share with patients that oral emergency contraceptive methods should not be used for long-term contraception (SOR: Good Practice Point, based on clinical experience of the guideline development group).

The Guttmacher Institute reports that without contraception, approximately 85% of sexually active women become pregnant each year.⁸ Long-acting reversible methods, such as implants and intrauterine devices, have annual pregnancy rates of 0.05% to 0.8%. With perfect (consistent and correct) use, combined oral contraceptives have a 0.3% annual pregnancy rate, but the rate rises to 9% with typical use. Condoms, when used perfectly, are associated with a 2% annual rate of pregnancy compared with an 18% rate with typical use.

ILLUSTRATIVE CASE

A 65-year-old woman is admitted to your inpatient service from your family health center. She is diagnosed with community-acquired pneumonia (CAP) based on a 5-day history of cough and fever and a positive chest x-ray. She now requires oxygen at rest. She has a past medical history of hypertension and diabetes, both of which have been controlled on oral medications. Antibiotic therapy is initiated for the treatment of the pneumonia, but what treatment duration is ideal?

The World Health Organization estimates that pneumonia is the third most common cause of mortality worldwide, causing 3.2 million deaths per year.² Appropriate prescribing of antibiotics is critical for the successful treatment of CAP.

The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) created consensus guidelines, published in 2007, for the treatment of CAP.³ These guidelines recommend a minimum 5-day course of antibiotics if the patient is clinically stable, which is defined as: afebrile for 48 hours, heart rate ≤100 beats/minute, respiratory rate ≤24 respirations/minute, systolic blood pressure ≥90 mm Hg, oxygen saturation ≥90%, normal mental status, and able to tolerate oral intake. Longer antibiotic treatment durations are recommended on an individualized basis, if, for example, the isolated pathogen is not susceptible to the initial antibiotic or if the infection was caused by an extrapulmonary source.

However, these recommendations are not routinely followed. Practitioners often make it their custom to prescribe longer courses of antibiotics.⁴ And yet we know that there are several reasons to consider shorter courses of antibiotics, including lower health care costs, fewer adverse effects, and lower rates of bacterial resistance.^5-7

Two meta-analyses were performed to compare the safety and efficacy of short- (≤7 days) vs long-course (>7 days) antibiotic therapy in CAP.^8,9 Both meta-analyses found no difference in efficacy or safety between shorter and longer courses of antibiotic treatment regimens for CAP. Secondary outcomes noted a trend toward decreased antibiotic-associated adverse events with shorter courses of therapy.^8,9

While these meta-analyses supported shorter courses of antibiotics for CAP, there are limitations to the broad implementation of their findings. Studies included in these analyses utilized a variety of antibiotic treatment regimens and longer courses (7 days vs 5 days) that are not recommended by the IDSA/ATS guidelines. Additionally, studies included both inpatient and outpatient treatment groups, so findings may not apply to an exclusively inpatient CAP population.^8,9

This study sought to validate the IDSA/ATS guidelines recommending a 5-day course of antibiotics for hospitalized patients with CAP.¹

STUDY SUMMARY

No differences in clinical outcomes between 5 days of Tx—and longer

This multicenter, double-blind, noninferiority randomized trial compared short-term antibiotic treatment duration (5 days) to physician-discretion antibiotic treatment duration among 312 patients ≥18 years of age admitted for CAP to one of 4 teaching hospitals in Spain.¹ Pneumonia was diagnosed on chest radiograph with at least one symptom: cough, fever, dyspnea, or chest pain. Patients were excluded if, among other things, they had an immunocompromising condition, lived in a nursing home, had a recent hospital stay, used antibiotics within the previous 30 days, or had an uncommon pathogen, such as Pseudomonas aeruginosa or Staphylococcus aureus.¹

This is the first study to support the efficacy of the 5-day course of antibiotics for hospitalized CAP patients recommended by IDSA/ATS guidelines.

Patients were randomized after receiving a minimum of 5 days of antibiotics to an intervention group (where, if clinically stable, no further antibiotics were given) or a control group (where physicians determined antibiotic duration).¹ Primary outcomes were clinical success rate at Days 10 and 30 from admission, defined as resolution of signs and symptoms of CAP without further antibiotics, and improvement of CAP-related symptoms as determined by an 18-item CAP symptom questionnaire. This questionnaire was scored 0 to 90, where higher scores indicated greater severity. Secondary outcomes included: duration of antibiotic use, time to clinical improvement, mortality, hospital readmission, hospital length of stay, and CAP recurrence.¹A total of 312 patients were randomized with 162 patients in the intervention group and 150 patients in the control group. The mean age of patients in the intervention and control groups was 66.2 and 64.7 years, respectively. Other baseline demographics were similar between the groups. Nearly 80% of patients received quinolone treatment; <10% received a beta-lactam plus a macrolide.¹

Clinical success rates were similar for the control and intervention groups, respectively, at Day 10 (49% vs 56%; P=.18) and Day 30 (89% vs 92%; P=.33). There was shorter median treatment duration with antibiotics in the intervention group compared with the control group (5 days vs 10 days; P<.001) and fewer 30-day hospital readmissions (1.4% vs 6.6%; P=.02). There were no differences for other secondary outcomes.¹

WHAT’S NEW

Clinical support for 2007 guidelines

This is the first study to clinically support the IDSA/ATS guidelines, which state that a 5-day course of antibiotic therapy for hospitalized adults with CAP is effective and without increased risk of adverse events.

CAVEATS

Generalizability to other meds and settings is unclear

This study focused on antibiotic duration for the treatment of CAP in hospitalized patients and mainly used quinolone antibiotics. It remains unclear if duration of therapy is as effective in the outpatient setting or when using alternative antibiotic regimens.

If patients continued to have symptoms (such as fever or low oxygen saturation on room air) after 5 days of antibiotic treatment, antibiotic treatment was continued in the study. Thus, patients in real life who continue to have symptoms may need individualized therapy and may require more than 5 days of antibiotics.

CHALLENGES TO IMPLEMENTATION

Antibiotics end before clinical improvement occurs

This study noted an average of 12 days in both groups for patients to achieve clinical improvement, with upwards of 15 to 18 days for patients to return to normal activity. Patients and providers may be dissatisfied if the treatment course ends days before clinical improvement of symptoms. This may cause prescribers to lengthen the duration of antibiotic therapy inappropriately.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 65-year-old woman is admitted to your inpatient service from your family health center. She is diagnosed with community-acquired pneumonia (CAP) based on a 5-day history of cough and fever and a positive chest x-ray. She now requires oxygen at rest. She has a past medical history of hypertension and diabetes, both of which have been controlled on oral medications. Antibiotic therapy is initiated for the treatment of the pneumonia, but what treatment duration is ideal?

The World Health Organization estimates that pneumonia is the third most common cause of mortality worldwide, causing 3.2 million deaths per year.² Appropriate prescribing of antibiotics is critical for the successful treatment of CAP.

The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) created consensus guidelines, published in 2007, for the treatment of CAP.³ These guidelines recommend a minimum 5-day course of antibiotics if the patient is clinically stable, which is defined as: afebrile for 48 hours, heart rate ≤100 beats/minute, respiratory rate ≤24 respirations/minute, systolic blood pressure ≥90 mm Hg, oxygen saturation ≥90%, normal mental status, and able to tolerate oral intake. Longer antibiotic treatment durations are recommended on an individualized basis, if, for example, the isolated pathogen is not susceptible to the initial antibiotic or if the infection was caused by an extrapulmonary source.

However, these recommendations are not routinely followed. Practitioners often make it their custom to prescribe longer courses of antibiotics.⁴ And yet we know that there are several reasons to consider shorter courses of antibiotics, including lower health care costs, fewer adverse effects, and lower rates of bacterial resistance.^5-7

Two meta-analyses were performed to compare the safety and efficacy of short- (≤7 days) vs long-course (>7 days) antibiotic therapy in CAP.^8,9 Both meta-analyses found no difference in efficacy or safety between shorter and longer courses of antibiotic treatment regimens for CAP. Secondary outcomes noted a trend toward decreased antibiotic-associated adverse events with shorter courses of therapy.^8,9

While these meta-analyses supported shorter courses of antibiotics for CAP, there are limitations to the broad implementation of their findings. Studies included in these analyses utilized a variety of antibiotic treatment regimens and longer courses (7 days vs 5 days) that are not recommended by the IDSA/ATS guidelines. Additionally, studies included both inpatient and outpatient treatment groups, so findings may not apply to an exclusively inpatient CAP population.^8,9

This study sought to validate the IDSA/ATS guidelines recommending a 5-day course of antibiotics for hospitalized patients with CAP.¹

STUDY SUMMARY

No differences in clinical outcomes between 5 days of Tx—and longer

This multicenter, double-blind, noninferiority randomized trial compared short-term antibiotic treatment duration (5 days) to physician-discretion antibiotic treatment duration among 312 patients ≥18 years of age admitted for CAP to one of 4 teaching hospitals in Spain.¹ Pneumonia was diagnosed on chest radiograph with at least one symptom: cough, fever, dyspnea, or chest pain. Patients were excluded if, among other things, they had an immunocompromising condition, lived in a nursing home, had a recent hospital stay, used antibiotics within the previous 30 days, or had an uncommon pathogen, such as Pseudomonas aeruginosa or Staphylococcus aureus.¹

This is the first study to support the efficacy of the 5-day course of antibiotics for hospitalized CAP patients recommended by IDSA/ATS guidelines.

Patients were randomized after receiving a minimum of 5 days of antibiotics to an intervention group (where, if clinically stable, no further antibiotics were given) or a control group (where physicians determined antibiotic duration).¹ Primary outcomes were clinical success rate at Days 10 and 30 from admission, defined as resolution of signs and symptoms of CAP without further antibiotics, and improvement of CAP-related symptoms as determined by an 18-item CAP symptom questionnaire. This questionnaire was scored 0 to 90, where higher scores indicated greater severity. Secondary outcomes included: duration of antibiotic use, time to clinical improvement, mortality, hospital readmission, hospital length of stay, and CAP recurrence.¹A total of 312 patients were randomized with 162 patients in the intervention group and 150 patients in the control group. The mean age of patients in the intervention and control groups was 66.2 and 64.7 years, respectively. Other baseline demographics were similar between the groups. Nearly 80% of patients received quinolone treatment; <10% received a beta-lactam plus a macrolide.¹

Clinical success rates were similar for the control and intervention groups, respectively, at Day 10 (49% vs 56%; P=.18) and Day 30 (89% vs 92%; P=.33). There was shorter median treatment duration with antibiotics in the intervention group compared with the control group (5 days vs 10 days; P<.001) and fewer 30-day hospital readmissions (1.4% vs 6.6%; P=.02). There were no differences for other secondary outcomes.¹

WHAT’S NEW

Clinical support for 2007 guidelines

This is the first study to clinically support the IDSA/ATS guidelines, which state that a 5-day course of antibiotic therapy for hospitalized adults with CAP is effective and without increased risk of adverse events.

CAVEATS

Generalizability to other meds and settings is unclear

This study focused on antibiotic duration for the treatment of CAP in hospitalized patients and mainly used quinolone antibiotics. It remains unclear if duration of therapy is as effective in the outpatient setting or when using alternative antibiotic regimens.

If patients continued to have symptoms (such as fever or low oxygen saturation on room air) after 5 days of antibiotic treatment, antibiotic treatment was continued in the study. Thus, patients in real life who continue to have symptoms may need individualized therapy and may require more than 5 days of antibiotics.

CHALLENGES TO IMPLEMENTATION

Antibiotics end before clinical improvement occurs

This study noted an average of 12 days in both groups for patients to achieve clinical improvement, with upwards of 15 to 18 days for patients to return to normal activity. Patients and providers may be dissatisfied if the treatment course ends days before clinical improvement of symptoms. This may cause prescribers to lengthen the duration of antibiotic therapy inappropriately.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 65-year-old woman is admitted to your inpatient service from your family health center. She is diagnosed with community-acquired pneumonia (CAP) based on a 5-day history of cough and fever and a positive chest x-ray. She now requires oxygen at rest. She has a past medical history of hypertension and diabetes, both of which have been controlled on oral medications. Antibiotic therapy is initiated for the treatment of the pneumonia, but what treatment duration is ideal?

The World Health Organization estimates that pneumonia is the third most common cause of mortality worldwide, causing 3.2 million deaths per year.² Appropriate prescribing of antibiotics is critical for the successful treatment of CAP.

The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) created consensus guidelines, published in 2007, for the treatment of CAP.³ These guidelines recommend a minimum 5-day course of antibiotics if the patient is clinically stable, which is defined as: afebrile for 48 hours, heart rate ≤100 beats/minute, respiratory rate ≤24 respirations/minute, systolic blood pressure ≥90 mm Hg, oxygen saturation ≥90%, normal mental status, and able to tolerate oral intake. Longer antibiotic treatment durations are recommended on an individualized basis, if, for example, the isolated pathogen is not susceptible to the initial antibiotic or if the infection was caused by an extrapulmonary source.

However, these recommendations are not routinely followed. Practitioners often make it their custom to prescribe longer courses of antibiotics.⁴ And yet we know that there are several reasons to consider shorter courses of antibiotics, including lower health care costs, fewer adverse effects, and lower rates of bacterial resistance.^5-7

Two meta-analyses were performed to compare the safety and efficacy of short- (≤7 days) vs long-course (>7 days) antibiotic therapy in CAP.^8,9 Both meta-analyses found no difference in efficacy or safety between shorter and longer courses of antibiotic treatment regimens for CAP. Secondary outcomes noted a trend toward decreased antibiotic-associated adverse events with shorter courses of therapy.^8,9

While these meta-analyses supported shorter courses of antibiotics for CAP, there are limitations to the broad implementation of their findings. Studies included in these analyses utilized a variety of antibiotic treatment regimens and longer courses (7 days vs 5 days) that are not recommended by the IDSA/ATS guidelines. Additionally, studies included both inpatient and outpatient treatment groups, so findings may not apply to an exclusively inpatient CAP population.^8,9

This study sought to validate the IDSA/ATS guidelines recommending a 5-day course of antibiotics for hospitalized patients with CAP.¹

STUDY SUMMARY

No differences in clinical outcomes between 5 days of Tx—and longer

This multicenter, double-blind, noninferiority randomized trial compared short-term antibiotic treatment duration (5 days) to physician-discretion antibiotic treatment duration among 312 patients ≥18 years of age admitted for CAP to one of 4 teaching hospitals in Spain.¹ Pneumonia was diagnosed on chest radiograph with at least one symptom: cough, fever, dyspnea, or chest pain. Patients were excluded if, among other things, they had an immunocompromising condition, lived in a nursing home, had a recent hospital stay, used antibiotics within the previous 30 days, or had an uncommon pathogen, such as Pseudomonas aeruginosa or Staphylococcus aureus.¹

This is the first study to support the efficacy of the 5-day course of antibiotics for hospitalized CAP patients recommended by IDSA/ATS guidelines.

Patients were randomized after receiving a minimum of 5 days of antibiotics to an intervention group (where, if clinically stable, no further antibiotics were given) or a control group (where physicians determined antibiotic duration).¹ Primary outcomes were clinical success rate at Days 10 and 30 from admission, defined as resolution of signs and symptoms of CAP without further antibiotics, and improvement of CAP-related symptoms as determined by an 18-item CAP symptom questionnaire. This questionnaire was scored 0 to 90, where higher scores indicated greater severity. Secondary outcomes included: duration of antibiotic use, time to clinical improvement, mortality, hospital readmission, hospital length of stay, and CAP recurrence.¹A total of 312 patients were randomized with 162 patients in the intervention group and 150 patients in the control group. The mean age of patients in the intervention and control groups was 66.2 and 64.7 years, respectively. Other baseline demographics were similar between the groups. Nearly 80% of patients received quinolone treatment; <10% received a beta-lactam plus a macrolide.¹

Clinical success rates were similar for the control and intervention groups, respectively, at Day 10 (49% vs 56%; P=.18) and Day 30 (89% vs 92%; P=.33). There was shorter median treatment duration with antibiotics in the intervention group compared with the control group (5 days vs 10 days; P<.001) and fewer 30-day hospital readmissions (1.4% vs 6.6%; P=.02). There were no differences for other secondary outcomes.¹

WHAT’S NEW

Clinical support for 2007 guidelines

This is the first study to clinically support the IDSA/ATS guidelines, which state that a 5-day course of antibiotic therapy for hospitalized adults with CAP is effective and without increased risk of adverse events.

CAVEATS

Generalizability to other meds and settings is unclear

This study focused on antibiotic duration for the treatment of CAP in hospitalized patients and mainly used quinolone antibiotics. It remains unclear if duration of therapy is as effective in the outpatient setting or when using alternative antibiotic regimens.

If patients continued to have symptoms (such as fever or low oxygen saturation on room air) after 5 days of antibiotic treatment, antibiotic treatment was continued in the study. Thus, patients in real life who continue to have symptoms may need individualized therapy and may require more than 5 days of antibiotics.

CHALLENGES TO IMPLEMENTATION

Antibiotics end before clinical improvement occurs

This study noted an average of 12 days in both groups for patients to achieve clinical improvement, with upwards of 15 to 18 days for patients to return to normal activity. Patients and providers may be dissatisfied if the treatment course ends days before clinical improvement of symptoms. This may cause prescribers to lengthen the duration of antibiotic therapy inappropriately.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

THE CASE

A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate (FIGURE). The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient’s medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.

THE DIAGNOSIS

The clinical diagnosis was erythroplakia. Trauma from food burn and inflammation of the salivary gland were both considered, but ultimately ruled out due to lack of symptoms and persistence of the lesion after 14 days. The pathology report confirmed a diagnosis of squamous cell carcinoma (SCC) in situ. Based on the pathology report, we referred the patient to an oral surgeon for wide surgical excision with evaluation of the margins.

Because of its location and subtle presentation, the lesion could have been easily overlooked, underscoring the importance of routinely going beyond dentition to examine the soft tissues of the mouth.

DISCUSSION

SCC is the most common cancer found in the oral cavity, accounting for 90% of all oral malignancies.^1,2 Other malignancies include lymphomas, sarcomas, melanomas, salivary gland neoplasms, and metastasis from other sites.^3,4 Predisposing factors include tobacco use (namely inhaled methods and chewing tobacco), alcohol misuse, human papillomavirus infection, and chewing betel nut.^1,5 (Betel nuts grow on a species of palm tree mainly found in India, Pakistan, and Bangladesh. They are commonly chewed for their caffeine-like effect and are known to be carcinogenic.)

Presentation. SCC of the oral cavity can have various presentations. The lesion can appear as white, red, a mix of white and red, as a mass, or as a nonhealing ulcer. While some patients may be asymptomatic (as was ours), some may have signs and symptoms such as pain, bleeding, difficulty swallowing, difficulty wearing dentures, or a neck mass.⁶ A history of smoking and alcohol misuse, which was present in this case, should heighten suspicion and prompt further investigation of oral lesions.

Location. The most common intraoral site for oral cancer is the tongue (on the posterolateral border) followed by the floor of the mouth. Other common sites in descending order are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.¹ (Our patient’s lesion was on the border of the hard and soft palate).

Treatment of oral cancer is surgical. In some cases, depending on the stage and size of the tumor, radiation and chemotherapy may be considered.^3,5 Approximately two-thirds of oral cancers are detected in the later stages.⁷ The 5-year survival rate for people with oral SCC found at stages III or IV ranges from 32% to 45%, while the rate for those with SCC detected at stages I or II is 58% to 72%.¹ Patients with a history of oral cancer have a 20-fold increased risk of a recurrence in the oral cavity or of developing cancer in the surrounding areas, such as the larynx, esophagus, and lungs, underscoring the necessity of adequate follow-up in these patients.^2,3,5

Who is at risk?

In 2015, there were an estimated 45,780 new cases of oral cavity and pharyngeal cancer and 8650 deaths from these causes.⁸ Although oral cancer accounts for only 3% of all cancers in the United States, it is the eighth most common cancer in males and the 15^th most common in females.¹ Prevalence differs tremendously by location, however. In India, for example, oral cancer accounts for 30% of all cancers.⁹ Regardless of location, incidence increases with age; 62 is the average age at diagnosis.² Oral cancers are also more common among African Americans than among Caucasians.^1,3,5

Smokers are 2 to 3 times more likely to develop oral cancer than nonsmokers.¹ This risk increases with amount and duration of smoking.¹ The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.^1,3

Alcohol use. Among male patients with oral cancer, one-third are heavy alcohol users.¹ In fact, one study found that 20% of these patients have cirrhosis of the liver.¹ Thus, it makes good clinical sense to routinely examine the soft tissue of the oral cavity for abnormalities in patients with alcohol-induced cirrhosis of the liver.

The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.

Our patient. We placed our patient on a 3-month recall and stressed the importance of not smoking. The patient had surgery and a good outcome was documented. The patient indicated at follow-up that he’d started drinking again and was referred for counseling.

TAKEAWAY

It’s important to pay attention to color differences in the oral cavity on routine visits, particularly in patients with known risk factors for SCC. Patients with a lesion in the oral cavity should be seen again within 2 weeks. If the lesion is unresolved, the patient should be referred for further examination and/or biopsy. The possibility of recurrent oral cancer or cancer in the surrounding areas makes these patients good candidates for frequent follow-up examinations.

We strongly suggest that primary care physicians encourage their patients with the known predisposing risk factors of tobacco use and chronic alcohol misuse to quit these habits, visit their dentists for annual oral cancer screenings, and report any oral symptoms promptly to their medical and/or dental care providers. The asymptomatic nature of many of these lesions underscores the importance of following this advice. As is the case with most other cancers, survival rate is dependent on the stage of the disease at diagnosis.

THE CASE

A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate (FIGURE). The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient’s medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.

THE DIAGNOSIS

The clinical diagnosis was erythroplakia. Trauma from food burn and inflammation of the salivary gland were both considered, but ultimately ruled out due to lack of symptoms and persistence of the lesion after 14 days. The pathology report confirmed a diagnosis of squamous cell carcinoma (SCC) in situ. Based on the pathology report, we referred the patient to an oral surgeon for wide surgical excision with evaluation of the margins.

Because of its location and subtle presentation, the lesion could have been easily overlooked, underscoring the importance of routinely going beyond dentition to examine the soft tissues of the mouth.

DISCUSSION

SCC is the most common cancer found in the oral cavity, accounting for 90% of all oral malignancies.^1,2 Other malignancies include lymphomas, sarcomas, melanomas, salivary gland neoplasms, and metastasis from other sites.^3,4 Predisposing factors include tobacco use (namely inhaled methods and chewing tobacco), alcohol misuse, human papillomavirus infection, and chewing betel nut.^1,5 (Betel nuts grow on a species of palm tree mainly found in India, Pakistan, and Bangladesh. They are commonly chewed for their caffeine-like effect and are known to be carcinogenic.)

Presentation. SCC of the oral cavity can have various presentations. The lesion can appear as white, red, a mix of white and red, as a mass, or as a nonhealing ulcer. While some patients may be asymptomatic (as was ours), some may have signs and symptoms such as pain, bleeding, difficulty swallowing, difficulty wearing dentures, or a neck mass.⁶ A history of smoking and alcohol misuse, which was present in this case, should heighten suspicion and prompt further investigation of oral lesions.

Location. The most common intraoral site for oral cancer is the tongue (on the posterolateral border) followed by the floor of the mouth. Other common sites in descending order are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.¹ (Our patient’s lesion was on the border of the hard and soft palate).

Treatment of oral cancer is surgical. In some cases, depending on the stage and size of the tumor, radiation and chemotherapy may be considered.^3,5 Approximately two-thirds of oral cancers are detected in the later stages.⁷ The 5-year survival rate for people with oral SCC found at stages III or IV ranges from 32% to 45%, while the rate for those with SCC detected at stages I or II is 58% to 72%.¹ Patients with a history of oral cancer have a 20-fold increased risk of a recurrence in the oral cavity or of developing cancer in the surrounding areas, such as the larynx, esophagus, and lungs, underscoring the necessity of adequate follow-up in these patients.^2,3,5

Who is at risk?

In 2015, there were an estimated 45,780 new cases of oral cavity and pharyngeal cancer and 8650 deaths from these causes.⁸ Although oral cancer accounts for only 3% of all cancers in the United States, it is the eighth most common cancer in males and the 15^th most common in females.¹ Prevalence differs tremendously by location, however. In India, for example, oral cancer accounts for 30% of all cancers.⁹ Regardless of location, incidence increases with age; 62 is the average age at diagnosis.² Oral cancers are also more common among African Americans than among Caucasians.^1,3,5

Smokers are 2 to 3 times more likely to develop oral cancer than nonsmokers.¹ This risk increases with amount and duration of smoking.¹ The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.^1,3

Alcohol use. Among male patients with oral cancer, one-third are heavy alcohol users.¹ In fact, one study found that 20% of these patients have cirrhosis of the liver.¹ Thus, it makes good clinical sense to routinely examine the soft tissue of the oral cavity for abnormalities in patients with alcohol-induced cirrhosis of the liver.

The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.

Our patient. We placed our patient on a 3-month recall and stressed the importance of not smoking. The patient had surgery and a good outcome was documented. The patient indicated at follow-up that he’d started drinking again and was referred for counseling.

TAKEAWAY

It’s important to pay attention to color differences in the oral cavity on routine visits, particularly in patients with known risk factors for SCC. Patients with a lesion in the oral cavity should be seen again within 2 weeks. If the lesion is unresolved, the patient should be referred for further examination and/or biopsy. The possibility of recurrent oral cancer or cancer in the surrounding areas makes these patients good candidates for frequent follow-up examinations.

We strongly suggest that primary care physicians encourage their patients with the known predisposing risk factors of tobacco use and chronic alcohol misuse to quit these habits, visit their dentists for annual oral cancer screenings, and report any oral symptoms promptly to their medical and/or dental care providers. The asymptomatic nature of many of these lesions underscores the importance of following this advice. As is the case with most other cancers, survival rate is dependent on the stage of the disease at diagnosis.

THE CASE

A 56-year-old white man presented at our dental clinic for routine care. The intraoral examination revealed an asymptomatic red lesion with white vesicle-like areas on the right side of the soft palate (FIGURE). The extraoral examination was normal, and regional lymph nodes were nonpalpable. The patient’s medical history included liver cirrhosis and pancreatitis. He also had a 30-year history of alcohol misuse (1-5 drinks per day) and a 30-pack-year smoking history. (The patient had stopped drinking at the time of presentation, and had quit smoking 2 years earlier.) We instructed him to gargle with warm salt water at home and return in 2 weeks. At follow-up, the lesion was unresolved, so a biopsy was performed.

THE DIAGNOSIS

The clinical diagnosis was erythroplakia. Trauma from food burn and inflammation of the salivary gland were both considered, but ultimately ruled out due to lack of symptoms and persistence of the lesion after 14 days. The pathology report confirmed a diagnosis of squamous cell carcinoma (SCC) in situ. Based on the pathology report, we referred the patient to an oral surgeon for wide surgical excision with evaluation of the margins.

Because of its location and subtle presentation, the lesion could have been easily overlooked, underscoring the importance of routinely going beyond dentition to examine the soft tissues of the mouth.

DISCUSSION

SCC is the most common cancer found in the oral cavity, accounting for 90% of all oral malignancies.^1,2 Other malignancies include lymphomas, sarcomas, melanomas, salivary gland neoplasms, and metastasis from other sites.^3,4 Predisposing factors include tobacco use (namely inhaled methods and chewing tobacco), alcohol misuse, human papillomavirus infection, and chewing betel nut.^1,5 (Betel nuts grow on a species of palm tree mainly found in India, Pakistan, and Bangladesh. They are commonly chewed for their caffeine-like effect and are known to be carcinogenic.)

Presentation. SCC of the oral cavity can have various presentations. The lesion can appear as white, red, a mix of white and red, as a mass, or as a nonhealing ulcer. While some patients may be asymptomatic (as was ours), some may have signs and symptoms such as pain, bleeding, difficulty swallowing, difficulty wearing dentures, or a neck mass.⁶ A history of smoking and alcohol misuse, which was present in this case, should heighten suspicion and prompt further investigation of oral lesions.

Location. The most common intraoral site for oral cancer is the tongue (on the posterolateral border) followed by the floor of the mouth. Other common sites in descending order are the soft palate, gingiva, buccal mucosa, labial mucosa, and hard palate.¹ (Our patient’s lesion was on the border of the hard and soft palate).

Treatment of oral cancer is surgical. In some cases, depending on the stage and size of the tumor, radiation and chemotherapy may be considered.^3,5 Approximately two-thirds of oral cancers are detected in the later stages.⁷ The 5-year survival rate for people with oral SCC found at stages III or IV ranges from 32% to 45%, while the rate for those with SCC detected at stages I or II is 58% to 72%.¹ Patients with a history of oral cancer have a 20-fold increased risk of a recurrence in the oral cavity or of developing cancer in the surrounding areas, such as the larynx, esophagus, and lungs, underscoring the necessity of adequate follow-up in these patients.^2,3,5

Who is at risk?

In 2015, there were an estimated 45,780 new cases of oral cavity and pharyngeal cancer and 8650 deaths from these causes.⁸ Although oral cancer accounts for only 3% of all cancers in the United States, it is the eighth most common cancer in males and the 15^th most common in females.¹ Prevalence differs tremendously by location, however. In India, for example, oral cancer accounts for 30% of all cancers.⁹ Regardless of location, incidence increases with age; 62 is the average age at diagnosis.² Oral cancers are also more common among African Americans than among Caucasians.^1,3,5

Smokers are 2 to 3 times more likely to develop oral cancer than nonsmokers.¹ This risk increases with amount and duration of smoking.¹ The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.^1,3

Alcohol use. Among male patients with oral cancer, one-third are heavy alcohol users.¹ In fact, one study found that 20% of these patients have cirrhosis of the liver.¹ Thus, it makes good clinical sense to routinely examine the soft tissue of the oral cavity for abnormalities in patients with alcohol-induced cirrhosis of the liver.

The combination of smoking and alcohol use has a synergistic effect, increasing the likelihood of developing oral cancer 15 fold.

Our patient. We placed our patient on a 3-month recall and stressed the importance of not smoking. The patient had surgery and a good outcome was documented. The patient indicated at follow-up that he’d started drinking again and was referred for counseling.

TAKEAWAY

It’s important to pay attention to color differences in the oral cavity on routine visits, particularly in patients with known risk factors for SCC. Patients with a lesion in the oral cavity should be seen again within 2 weeks. If the lesion is unresolved, the patient should be referred for further examination and/or biopsy. The possibility of recurrent oral cancer or cancer in the surrounding areas makes these patients good candidates for frequent follow-up examinations.

We strongly suggest that primary care physicians encourage their patients with the known predisposing risk factors of tobacco use and chronic alcohol misuse to quit these habits, visit their dentists for annual oral cancer screenings, and report any oral symptoms promptly to their medical and/or dental care providers. The asymptomatic nature of many of these lesions underscores the importance of following this advice. As is the case with most other cancers, survival rate is dependent on the stage of the disease at diagnosis.

It depends on whom you ask. But if you ask me, obesity should not be labeled a disease.

I understand the rationale for calling obesity a disease—it helps legitimize the time we spend treating obesity and aids in getting paid for that time. Some people have distinct diseases, such as Prader-Willi syndrome, hypothyroidism, and Cushing’s syndrome that can cause obesity, and perhaps massive obesity is best categorized and treated as a disease. But the “garden variety” obesity that affects nearly 40% of the US adult population¹ behaves more like a risk factor than a disease. Think of other continuous variables like blood pressure and cholesterol—the higher the measurement, the higher the risk of a plethora of medical problems.

Obesity is a global public health problem that is due largely—at least in this country—to the widespread availability of inexpensive, calorie-packed foods, as well as a desire by a screen-addicted society to stay home and “play” online rather than outdoors. Obesity is a health risk factor produced by our current social milieu and modified by genetics and personal health habits.

Remember that a 5% to 10% weight loss is beneficial—especially for patients with diabetes.

So what can we do? We need to recognize our limited, but important, role and remain nonjudgmental with our overweight and obese patients when they are unsuccessful at losing weight. It is easy to play the blame game, even in subtle ways. Recognizing that obesity is more of a social issue than a personal behavioral issue is a great place to start. Asking patients what they want to do and helping them set goals and find the resources to reach their goals can be helpful. Celebrating even small decreases in weight or increases in physical activity is always good medicine. Remember that a 5% to 10% weight loss has medically beneficial effects, especially for patients with diabetes.²

In addition to recommendations (and referrals) to help patients reduce calories and increase exercise, we have other weight-loss tools to draw upon. Gastric bypass surgery is certainly effective—especially for obese patients with diabetes. And while medication is no replacement for proper diet and exercise, it is another option to consider. Randomized trials have demonstrated some effectiveness for up to 4 years, although no long-term trials (lasting ≥5 years) have been performed. (See “Obesity: When to consider medication.”)

So whether you consider obesity a disease, or not, we now have even more ways with which to combat it.

It depends on whom you ask. But if you ask me, obesity should not be labeled a disease.

I understand the rationale for calling obesity a disease—it helps legitimize the time we spend treating obesity and aids in getting paid for that time. Some people have distinct diseases, such as Prader-Willi syndrome, hypothyroidism, and Cushing’s syndrome that can cause obesity, and perhaps massive obesity is best categorized and treated as a disease. But the “garden variety” obesity that affects nearly 40% of the US adult population¹ behaves more like a risk factor than a disease. Think of other continuous variables like blood pressure and cholesterol—the higher the measurement, the higher the risk of a plethora of medical problems.

Obesity is a global public health problem that is due largely—at least in this country—to the widespread availability of inexpensive, calorie-packed foods, as well as a desire by a screen-addicted society to stay home and “play” online rather than outdoors. Obesity is a health risk factor produced by our current social milieu and modified by genetics and personal health habits.

Remember that a 5% to 10% weight loss is beneficial—especially for patients with diabetes.

So what can we do? We need to recognize our limited, but important, role and remain nonjudgmental with our overweight and obese patients when they are unsuccessful at losing weight. It is easy to play the blame game, even in subtle ways. Recognizing that obesity is more of a social issue than a personal behavioral issue is a great place to start. Asking patients what they want to do and helping them set goals and find the resources to reach their goals can be helpful. Celebrating even small decreases in weight or increases in physical activity is always good medicine. Remember that a 5% to 10% weight loss has medically beneficial effects, especially for patients with diabetes.²

In addition to recommendations (and referrals) to help patients reduce calories and increase exercise, we have other weight-loss tools to draw upon. Gastric bypass surgery is certainly effective—especially for obese patients with diabetes. And while medication is no replacement for proper diet and exercise, it is another option to consider. Randomized trials have demonstrated some effectiveness for up to 4 years, although no long-term trials (lasting ≥5 years) have been performed. (See “Obesity: When to consider medication.”)

So whether you consider obesity a disease, or not, we now have even more ways with which to combat it.

It depends on whom you ask. But if you ask me, obesity should not be labeled a disease.

I understand the rationale for calling obesity a disease—it helps legitimize the time we spend treating obesity and aids in getting paid for that time. Some people have distinct diseases, such as Prader-Willi syndrome, hypothyroidism, and Cushing’s syndrome that can cause obesity, and perhaps massive obesity is best categorized and treated as a disease. But the “garden variety” obesity that affects nearly 40% of the US adult population¹ behaves more like a risk factor than a disease. Think of other continuous variables like blood pressure and cholesterol—the higher the measurement, the higher the risk of a plethora of medical problems.

Obesity is a global public health problem that is due largely—at least in this country—to the widespread availability of inexpensive, calorie-packed foods, as well as a desire by a screen-addicted society to stay home and “play” online rather than outdoors. Obesity is a health risk factor produced by our current social milieu and modified by genetics and personal health habits.

Remember that a 5% to 10% weight loss is beneficial—especially for patients with diabetes.

So what can we do? We need to recognize our limited, but important, role and remain nonjudgmental with our overweight and obese patients when they are unsuccessful at losing weight. It is easy to play the blame game, even in subtle ways. Recognizing that obesity is more of a social issue than a personal behavioral issue is a great place to start. Asking patients what they want to do and helping them set goals and find the resources to reach their goals can be helpful. Celebrating even small decreases in weight or increases in physical activity is always good medicine. Remember that a 5% to 10% weight loss has medically beneficial effects, especially for patients with diabetes.²

In addition to recommendations (and referrals) to help patients reduce calories and increase exercise, we have other weight-loss tools to draw upon. Gastric bypass surgery is certainly effective—especially for obese patients with diabetes. And while medication is no replacement for proper diet and exercise, it is another option to consider. Randomized trials have demonstrated some effectiveness for up to 4 years, although no long-term trials (lasting ≥5 years) have been performed. (See “Obesity: When to consider medication.”)

So whether you consider obesity a disease, or not, we now have even more ways with which to combat it.

THE CASE

DeSean W,* a 47-year-old man, returned to his primary care clinic with a new complaint of epigastric burning that had been bothering him for the past 4 months. He had tried several over-the-counter remedies, which provided no relief. He also remained concerned—despite assurances to the contrary at previous clinic visits—that he had contracted a sexually-transmitted disease (STD) after going to a bar one night 4 to 5 months ago. At 2 other clinic visits since that time, STD test results were negative. At this current visit, symptoms and details of sexual history were unchanged since the last visit, with the exception of the epigastric pain.

When asked if he thought he had contracted an STD through a sexual encounter the night he went to the bar, he emphatically said he would not cheat on his wife. Surprisingly, given his concern, he avoided further discussion on modes of contracting an STD.

The physician prescribed ranitidine 150 mg bid for the epigastric burning and explained, once more, the significance of the STD test results. However, he also decided to further examine Mr. W’s concern about STDs and the night he may have contracted one.

HOW WOULD YOU PROCEED WITH THIS PATIENT?

*The patient’s name has been changed to protect his privacy.

SCOPE OF THE PROBLEM

Despite being as common as asthma, posttraumatic stress disorder (PTSD) often remains undiagnosed and untreated in primary care.¹ In brief, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines PTSD as persistent and long-term changes in thoughts or mood following actual or threatened exposure to death, serious injury, or sexual assault that leads to re-experiencing, functional impairment, physiologic stress reactions, and avoidance of thoughts or situations associated with the original trauma.² More than one in 10 women and one in 20 men experience PTSD in their lifetime.^2,3 Population-based studies have not yet determined the prevalence among children.³ Almost 40% of US adults report having experienced a trauma before age 13, and about one-third of these go on to develop PTSD.⁴

Individuals with PTSD have higher rates of somatic complaints, overall medical utilization, prescription use, physical and social disability, attempted suicide, and all-cause mortality.^3,5-7 PTSD is associated with increased risk for cardiac, gastrointestinal, metabolic, and immunologic illnesses, other psychiatric illnesses, risky health behaviors, and decreased medical adherence.^4,6 Additionally, prevention and treatment efforts for STDs and obesity are less effective among those with trauma histories.⁴ Thus, detection and treatment of PTSD improves the likelihood of successfully treating other health concerns.

THE ESSENTIALS OF A PTSD DIAGNOSIS

DSM-5 diagnosis of PTSD requires the experience of a trauma and resultant symptoms from each of 4 symptom-clusters:²

• one or more re-experiencing symptoms (eg, intrusive memories or recurrent distressing dreams, psychological distress or physiologic reactions to reminders of the trauma)
• one or more avoidance symptoms (eg, avoidance of trauma memories or of people and places that trigger a reminder of the trauma)
• two or more changes in thoughts or mood (eg, negative beliefs about self or others, social detachment, anhedonia)
• two or more changes in arousal activity (eg, sleep problems, hypervigilance, inability to concentrate).

Since many people experiencing traumas do not develop PTSD,^5,8 symptoms must last at least one month to meet the criteria for diagnosis.² Sexual trauma, experiencing multiple traumas, and lack of social support increase the risk that an individual will develop PTSD.^9-11 Notably, symptom onset will be delayed 6 months or more in some individuals,^2,8 making it more difficult for those patients and clinicians to connect symptoms to the trauma.¹²

Differential diagnosis

PTSD must be differentiated from other mental health conditions with overlapping symptoms (TABLE 1^2,8,13), but it may also be comorbid with one or more of these other conditions. When patients with PTSD do report mental health symptoms, providers often focus on the depressive symptoms that overlap with PTSD, and on substance use, which often accompanies PTSD, leaving PTSD undetected.⁹

Given that depressed/irritable mood, decreased participation in pleasurable activities, negative views of the world, attention difficulties, sleep difficulties, feelings of guilt, and agitation/restlessness are symptoms of both depression and PTSD,² it is particularly important to screen patients with depressive symptoms for trauma history.

Why PTSD is often missed

Due to the impact of PTSD on overall health, the rates of PTSD in primary care clinics may be higher than in the general population.¹⁴ Thus, primary care clinicians are likely seeing PTSD more often than they realize. In fact, a systematic review showed that clinicians detected 0% to 52% of their patients with PTSD, missing at least half of all PTSD diagnoses.⁹

Prevention and treatment efforts for STDs and obesity are less effective among those with trauma histories.

Detecting PTSD can be challenging for several reasons. Symptoms can span the emotional, social, physical, and behavioral aspects of an individual’s life, so patients and clinicians alike may regard symptoms as unrelated to PTSD.⁸ Primary symptom presentation may vary, with some people reporting anxiety symptoms, others mostly depressive symptoms, and others arousal, dissociative, or—as in our patient’s case—somatic symptoms.² In affected children, parents may report emotional or behavioral problems without mentioning the trauma.² Additionally, for traumas that were not a single event, such as long-term child abuse, patients may have difficulty identifying symptom onset.²

CASE

The physician screened Mr. W for trauma exposure as part of the differential. Mr. W revealed that he had blacked out at the bar, despite drinking only moderately, and that he awoke with anal pain. He believed he had been drugged and sexually assaulted. Further screening for PTSD symptoms related to this event confirmed multiple associated symptoms. He acknowledged that his epigastric pain had started soon after the trauma and, after further discussion, began to link his stomach pain and other new symptoms revealed by the PTSD screen (hypervigilance, avoidance, change in mood) to the trauma.

As happened in this case, most PTSD patients present with somatic complaints rather than reporting a traumatic experience and having associated effects. This in turn usually leads clinicians to consider only non-PTSD diagnoses.^6,9,15 Core avoidance symptoms are a major reason for such a presentation in PTSD patients.¹⁴ Patients avoid thoughts, feelings, and conversations that remind them of the trauma.¹³ As a result, they are less likely to voluntarily report trauma. They avoid thinking about how their current symptoms may be associated with their trauma and are reluctant to talk about their trauma with clinicians.^5,9,8,12

Another barrier to diagnosis is a belief that PTSD is primarily experienced by combat veterans¹ (TABLE 2^{2,4-6,8,9,12,14-18}). While PTSD is detected more often among veterans due to regular screening through the Department of Veterans Affairs,¹⁴ the vast majority of PTSD cases are related to civilian traumas such as sexual assault, child abuse, and car accidents.^5,9 In fact, the estimated 9% prevalence¹⁶ of PTSD among the 18.8 million US veterans¹⁷ (1.7 million veterans with PTSD) accounts for less than 10% of the total lifetime prevalence² of PTSD in the US population (27.9 million people with PTSD).¹⁸


SCREENING: WHAT TO LOOK FOR

Since individuals with PTSD mainly seek treatment for associated physical symptoms,¹⁴ primary care is particularly important for identification of PTSD and treatment access. The US Preventative Services Task Force does not yet have any recommendations for screening for PTSD. The American Psychiatric Association recommends that a trauma history be included in all initial psychiatric evaluations of adults.¹⁹ Screens can target high-risk populations and can be repeated across the lifespan,⁹ as traumas can occur at any age and symptoms may not emerge until years after the trauma.^2,4 Factors in a patient’s history associated with high risk of PTSD include the following:

• known trauma exposure (eg, treatment at the emergency department following motor vehicle collision, natural disaster, assault),⁶
• frequent medical visits or unexplained physical symptoms,^5,8
• family members who are trauma victims,⁸
• involvement in juvenile justice system,^4,12
• sensitive or invasive exams (eg, pelvic exams) that trigger symptoms or contribute to retraumatization,^12,20 and
• any medical condition (eg, hypertension, chronic pain, sleep disorder), self-destructive behavior (eg, drug or alcohol abuse, low impulse control), or social/occupational issues (eg, unemployment, social isolation, fighting) with a known link to PTSD.^2,4,6,8

The first step in screening. Given a patient’s reported symptoms, assess for trauma exposure to determine whether PTSD should be included in the differential diagnosis. Overlooking PTSD as a possible source of symptoms can result in misattributing them to other causes.^4,8 Listing common traumas, or using a standardized list such as the Life Events Checklist, can help identify patients with trauma exposure.^8,21 However, do not make the patient provide details of the traumatic event(s), as that can exacerbate symptoms if PTSD is present.⁶ It is sufficient to know the category of the trauma (eg, sexual assault) without making the patient describe who was involved and what happened.⁶

The second step in screening. If a patient reveals trauma exposure, consider using an instrument such as the Primary Care PTSD Screen (PC-PTSD) or the PTSD Checklist, both available online, to screen for PTSD symptoms related to the identified trauma.^6,9,21-23 Since these measures screen for symptoms but do not ask about trauma exposure, false positives can occur if a trauma is not first identified (such as through the Life Events Checklist) due to symptom overlap with other conditions (TABLE 1^2,8,13).²¹

Treatment is effective, even decades after a traumatic event

Provide anyone who has been traumatized with information about common after effects, symptoms of PTSD, and available treatments.⁸ Keep in mind that initial symptom severity after trauma exposure does not correlate with long-term symptoms,⁸ and about half of adults will recover without treatment within 3 months.^1,2,5 The first month of symptoms may be addressed with patient education and watchful waiting. But if symptoms don’t subside after a month, consider offering treatment¹ with the understanding that, for some individuals, symptoms may yet resolve on their own.

Detecting and treating PTSD early can decrease its deleterious effects on health and cut down on years of functional impairment.¹ Even decades after an initial traumatic event, PTSD treatments can be effective.⁸ Children may experience functional impairment without meeting full criteria for PTSD, and can also benefit from treatment.⁷

INTEGRATING EXPOSURE AND COGNITIVE THERAPIES IS KEY

Offer any patient who meets criteria for PTSD a referral for exposure therapy and trauma-focused cognitive behavioral therapy (TF-CBT), the first-line treatments for PTSD.^1,4,8,24,25

Exposure therapies for PTSD are supported by strong evidence and help patients to become desensitized to distressful memories through gradual, repeated exposures in a relaxed or safe space.^8,26

Cognitive methods, such as cognitive processing therapy, cognitive behavioral therapy, and cognitive reprocessing have moderate strength of evidence, and may be combined with exposure therapy.²⁶ Cognitive therapies help patients change thoughts, beliefs, and behaviors that contribute to PTSD symptoms.^8,26

Exposure and TF-CBT have the most empirical evidence for child, adolescent, and adult PTSD, and are effective for the range of PTSD symptoms,^4,8,25 including avoidance—a fundamental component of PTSD that drives other PTSD symptoms²⁷—comorbid depression, and other emotions associated with trauma (eg, shame, guilt, and anger).^8,25 Family involvement is recommended for children and adolescents.⁴

Screen for a history of trauma in any patient who has depressive symptoms.

For patients with comorbid substance abuse, offer integrated PTSD/substance abuse treatment, which is more effective than isolated treatment of each.⁴ Relaxation training can be helpful as an adjunct to TF-CBT, but is not sufficient as a stand-alone treatment.¹³ Other psychotherapies, such as supportive, psychodynamic, systemic, and hypnotherapy, have not proved effective.¹⁴

Eye Movement Desensitization and Reprocessing (EMDR), a much publicized but controversial treatment, integrates components of exposure and cognitive therapies with therapist-directed eye movements.^28-30 Patients imagine their trauma while the therapist directs their eye movements, which is thought to provide exposure to trauma images and memories, thereby reducing symptoms. EMDR has been found to reduce PTSD symptoms with a low to moderate strength-of-evidence rating.²⁶ However, it has not proved more effective than other exposure and cognitive therapies, and its unique component (eg, eye movements) has not added any effect to outcomes.^28-31

Other newer therapies, such as Acceptance and Commitment Therapy^7,24,27 and online and computer-assisted treatments, are being evaluated.¹⁴

Medications take on an adjunct role to therapy

Drug treatment of PTSD has not been effective in children or adolescents.^4,8 In adults, medications have helped relieve some symptoms of PTSD. However, given their low effect sizes, medications are not recommended as first-line treatments over exposure and TF-CBT. Their usefulness lies chiefly in an adjunct role to exposure and cognitive therapies or for patients who refuse psychotherapy.^4,8,25

Selective serotonin reuptake inhibitors such as fluoxetine, paroxetine, and sertraline, have been effective for such PTSD symptoms as intrusive thoughts, negative or irritable mood, anxiety, restlessness, attention difficulties, and hyperarousal.^1,8

While benzodiazepines have been used to control anxiety, hyperarousal, and insomnia, they have not been effective for most other PTSD symptoms, including avoidance, re-experiencing, and cognitive symptoms. Furthermore, they are not recommended given their augmentative effect on other related symptoms and associated conditions (eg, dissociation, disinhibition, substance abuse) and possible interference with desensitization that occurs in exposure therapy.^1,5

While PTSD is detected more often among veterans, due to regular screening through the VA system, most cases are related to civilian traumas, such as sexual assault.

If a patient has significant insomnia and PTSD-related nightmares, consider starting prazosin at 1 mg/d and titrating up to an effective dose, which typically ranges from 5 to 20 mg per day.^1,5 Additionally, trazodone or antihistamines may be used to enhance sleep.¹

COORDINATION OF CARE

Upon identifying PTSD and offering treatment, introduce the patient to a mental health provider as part of the referral process, which strongly encourages patient engagement in treatment.¹⁴ Collaborate with the psychotherapist throughout treatment to facilitate a biopsychosocial approach to the patient’s care, and coordinate the monitoring and treatment of any comorbid physical conditions.

The Substance Abuse and Mental Health Services Administration has proposed a framework for multisystem Trauma-Informed Care (TIC), in which the primary care physician has many roles, including:^12,20

• recording or communicating sensitive private information to other providers through the electronic medical record in a manner that does not interfere with a patient’s development of trust or lead to exposure and retraumatization,
• performing invasive physical exams in a sensitive and patient-centered manner, and
• using support and shared decision-making in clinical encounters.

Physicians can also connect patients with PTSD to programs or groups that aid in developing resilience, such as physical exercise classes, social support networks, and community involvement opportunities.⁴

CASE

The physician referred Mr. W to an onsite psychologist. At a subsequent clinic visit in which he was seen by a different primary care physician, Mr. W expressed new concerns about shoulder pain and changes in a mole. During this visit, Mr. W was asked whether he had followed up on the earlier referral for counseling. He replied that he had attended an intake appointment with the psychologist, but that he had not wanted to talk about what had happened to him and therefore avoided future appointments.*

He remained concerned that he might have an STD, but declined medication for PTSD because he felt he was “moving on” with his life.

*Author’s note: Getting patients to open up about their trauma exposure can be difficult. If the patient isn’t ready, simply bringing up the experience can trigger avoidance. It’s often helpful to encourage patients to first develop a relationship with their therapist, then later discuss the details of their trauma when they are ready. This encourages patients to engage in the counseling process.

CORRESPONDENCE
Adrienne A. Williams, PhD, Department of Family Medicine, University of Illinois at Chicago College of Medicine, 1919 W Taylor Street, MC663, Chicago, IL 60612; [email protected].

THE CASE

DeSean W,* a 47-year-old man, returned to his primary care clinic with a new complaint of epigastric burning that had been bothering him for the past 4 months. He had tried several over-the-counter remedies, which provided no relief. He also remained concerned—despite assurances to the contrary at previous clinic visits—that he had contracted a sexually-transmitted disease (STD) after going to a bar one night 4 to 5 months ago. At 2 other clinic visits since that time, STD test results were negative. At this current visit, symptoms and details of sexual history were unchanged since the last visit, with the exception of the epigastric pain.

When asked if he thought he had contracted an STD through a sexual encounter the night he went to the bar, he emphatically said he would not cheat on his wife. Surprisingly, given his concern, he avoided further discussion on modes of contracting an STD.

The physician prescribed ranitidine 150 mg bid for the epigastric burning and explained, once more, the significance of the STD test results. However, he also decided to further examine Mr. W’s concern about STDs and the night he may have contracted one.

HOW WOULD YOU PROCEED WITH THIS PATIENT?

*The patient’s name has been changed to protect his privacy.

SCOPE OF THE PROBLEM

Despite being as common as asthma, posttraumatic stress disorder (PTSD) often remains undiagnosed and untreated in primary care.¹ In brief, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines PTSD as persistent and long-term changes in thoughts or mood following actual or threatened exposure to death, serious injury, or sexual assault that leads to re-experiencing, functional impairment, physiologic stress reactions, and avoidance of thoughts or situations associated with the original trauma.² More than one in 10 women and one in 20 men experience PTSD in their lifetime.^2,3 Population-based studies have not yet determined the prevalence among children.³ Almost 40% of US adults report having experienced a trauma before age 13, and about one-third of these go on to develop PTSD.⁴

Individuals with PTSD have higher rates of somatic complaints, overall medical utilization, prescription use, physical and social disability, attempted suicide, and all-cause mortality.^3,5-7 PTSD is associated with increased risk for cardiac, gastrointestinal, metabolic, and immunologic illnesses, other psychiatric illnesses, risky health behaviors, and decreased medical adherence.^4,6 Additionally, prevention and treatment efforts for STDs and obesity are less effective among those with trauma histories.⁴ Thus, detection and treatment of PTSD improves the likelihood of successfully treating other health concerns.

THE ESSENTIALS OF A PTSD DIAGNOSIS

DSM-5 diagnosis of PTSD requires the experience of a trauma and resultant symptoms from each of 4 symptom-clusters:²

• one or more re-experiencing symptoms (eg, intrusive memories or recurrent distressing dreams, psychological distress or physiologic reactions to reminders of the trauma)
• one or more avoidance symptoms (eg, avoidance of trauma memories or of people and places that trigger a reminder of the trauma)
• two or more changes in thoughts or mood (eg, negative beliefs about self or others, social detachment, anhedonia)
• two or more changes in arousal activity (eg, sleep problems, hypervigilance, inability to concentrate).

Since many people experiencing traumas do not develop PTSD,^5,8 symptoms must last at least one month to meet the criteria for diagnosis.² Sexual trauma, experiencing multiple traumas, and lack of social support increase the risk that an individual will develop PTSD.^9-11 Notably, symptom onset will be delayed 6 months or more in some individuals,^2,8 making it more difficult for those patients and clinicians to connect symptoms to the trauma.¹²

Differential diagnosis

PTSD must be differentiated from other mental health conditions with overlapping symptoms (TABLE 1^2,8,13), but it may also be comorbid with one or more of these other conditions. When patients with PTSD do report mental health symptoms, providers often focus on the depressive symptoms that overlap with PTSD, and on substance use, which often accompanies PTSD, leaving PTSD undetected.⁹

Given that depressed/irritable mood, decreased participation in pleasurable activities, negative views of the world, attention difficulties, sleep difficulties, feelings of guilt, and agitation/restlessness are symptoms of both depression and PTSD,² it is particularly important to screen patients with depressive symptoms for trauma history.

Why PTSD is often missed

Due to the impact of PTSD on overall health, the rates of PTSD in primary care clinics may be higher than in the general population.¹⁴ Thus, primary care clinicians are likely seeing PTSD more often than they realize. In fact, a systematic review showed that clinicians detected 0% to 52% of their patients with PTSD, missing at least half of all PTSD diagnoses.⁹

Prevention and treatment efforts for STDs and obesity are less effective among those with trauma histories.

Detecting PTSD can be challenging for several reasons. Symptoms can span the emotional, social, physical, and behavioral aspects of an individual’s life, so patients and clinicians alike may regard symptoms as unrelated to PTSD.⁸ Primary symptom presentation may vary, with some people reporting anxiety symptoms, others mostly depressive symptoms, and others arousal, dissociative, or—as in our patient’s case—somatic symptoms.² In affected children, parents may report emotional or behavioral problems without mentioning the trauma.² Additionally, for traumas that were not a single event, such as long-term child abuse, patients may have difficulty identifying symptom onset.²

CASE

The physician screened Mr. W for trauma exposure as part of the differential. Mr. W revealed that he had blacked out at the bar, despite drinking only moderately, and that he awoke with anal pain. He believed he had been drugged and sexually assaulted. Further screening for PTSD symptoms related to this event confirmed multiple associated symptoms. He acknowledged that his epigastric pain had started soon after the trauma and, after further discussion, began to link his stomach pain and other new symptoms revealed by the PTSD screen (hypervigilance, avoidance, change in mood) to the trauma.

As happened in this case, most PTSD patients present with somatic complaints rather than reporting a traumatic experience and having associated effects. This in turn usually leads clinicians to consider only non-PTSD diagnoses.^6,9,15 Core avoidance symptoms are a major reason for such a presentation in PTSD patients.¹⁴ Patients avoid thoughts, feelings, and conversations that remind them of the trauma.¹³ As a result, they are less likely to voluntarily report trauma. They avoid thinking about how their current symptoms may be associated with their trauma and are reluctant to talk about their trauma with clinicians.^5,9,8,12

Another barrier to diagnosis is a belief that PTSD is primarily experienced by combat veterans¹ (TABLE 2^{2,4-6,8,9,12,14-18}). While PTSD is detected more often among veterans due to regular screening through the Department of Veterans Affairs,¹⁴ the vast majority of PTSD cases are related to civilian traumas such as sexual assault, child abuse, and car accidents.^5,9 In fact, the estimated 9% prevalence¹⁶ of PTSD among the 18.8 million US veterans¹⁷ (1.7 million veterans with PTSD) accounts for less than 10% of the total lifetime prevalence² of PTSD in the US population (27.9 million people with PTSD).¹⁸


SCREENING: WHAT TO LOOK FOR

Since individuals with PTSD mainly seek treatment for associated physical symptoms,¹⁴ primary care is particularly important for identification of PTSD and treatment access. The US Preventative Services Task Force does not yet have any recommendations for screening for PTSD. The American Psychiatric Association recommends that a trauma history be included in all initial psychiatric evaluations of adults.¹⁹ Screens can target high-risk populations and can be repeated across the lifespan,⁹ as traumas can occur at any age and symptoms may not emerge until years after the trauma.^2,4 Factors in a patient’s history associated with high risk of PTSD include the following:

• known trauma exposure (eg, treatment at the emergency department following motor vehicle collision, natural disaster, assault),⁶
• frequent medical visits or unexplained physical symptoms,^5,8
• family members who are trauma victims,⁸
• involvement in juvenile justice system,^4,12
• sensitive or invasive exams (eg, pelvic exams) that trigger symptoms or contribute to retraumatization,^12,20 and
• any medical condition (eg, hypertension, chronic pain, sleep disorder), self-destructive behavior (eg, drug or alcohol abuse, low impulse control), or social/occupational issues (eg, unemployment, social isolation, fighting) with a known link to PTSD.^2,4,6,8

The first step in screening. Given a patient’s reported symptoms, assess for trauma exposure to determine whether PTSD should be included in the differential diagnosis. Overlooking PTSD as a possible source of symptoms can result in misattributing them to other causes.^4,8 Listing common traumas, or using a standardized list such as the Life Events Checklist, can help identify patients with trauma exposure.^8,21 However, do not make the patient provide details of the traumatic event(s), as that can exacerbate symptoms if PTSD is present.⁶ It is sufficient to know the category of the trauma (eg, sexual assault) without making the patient describe who was involved and what happened.⁶

The second step in screening. If a patient reveals trauma exposure, consider using an instrument such as the Primary Care PTSD Screen (PC-PTSD) or the PTSD Checklist, both available online, to screen for PTSD symptoms related to the identified trauma.^6,9,21-23 Since these measures screen for symptoms but do not ask about trauma exposure, false positives can occur if a trauma is not first identified (such as through the Life Events Checklist) due to symptom overlap with other conditions (TABLE 1^2,8,13).²¹

Treatment is effective, even decades after a traumatic event

Provide anyone who has been traumatized with information about common after effects, symptoms of PTSD, and available treatments.⁸ Keep in mind that initial symptom severity after trauma exposure does not correlate with long-term symptoms,⁸ and about half of adults will recover without treatment within 3 months.^1,2,5 The first month of symptoms may be addressed with patient education and watchful waiting. But if symptoms don’t subside after a month, consider offering treatment¹ with the understanding that, for some individuals, symptoms may yet resolve on their own.

Detecting and treating PTSD early can decrease its deleterious effects on health and cut down on years of functional impairment.¹ Even decades after an initial traumatic event, PTSD treatments can be effective.⁸ Children may experience functional impairment without meeting full criteria for PTSD, and can also benefit from treatment.⁷

INTEGRATING EXPOSURE AND COGNITIVE THERAPIES IS KEY

Offer any patient who meets criteria for PTSD a referral for exposure therapy and trauma-focused cognitive behavioral therapy (TF-CBT), the first-line treatments for PTSD.^1,4,8,24,25

Exposure therapies for PTSD are supported by strong evidence and help patients to become desensitized to distressful memories through gradual, repeated exposures in a relaxed or safe space.^8,26

Cognitive methods, such as cognitive processing therapy, cognitive behavioral therapy, and cognitive reprocessing have moderate strength of evidence, and may be combined with exposure therapy.²⁶ Cognitive therapies help patients change thoughts, beliefs, and behaviors that contribute to PTSD symptoms.^8,26

Exposure and TF-CBT have the most empirical evidence for child, adolescent, and adult PTSD, and are effective for the range of PTSD symptoms,^4,8,25 including avoidance—a fundamental component of PTSD that drives other PTSD symptoms²⁷—comorbid depression, and other emotions associated with trauma (eg, shame, guilt, and anger).^8,25 Family involvement is recommended for children and adolescents.⁴

Screen for a history of trauma in any patient who has depressive symptoms.

For patients with comorbid substance abuse, offer integrated PTSD/substance abuse treatment, which is more effective than isolated treatment of each.⁴ Relaxation training can be helpful as an adjunct to TF-CBT, but is not sufficient as a stand-alone treatment.¹³ Other psychotherapies, such as supportive, psychodynamic, systemic, and hypnotherapy, have not proved effective.¹⁴

Eye Movement Desensitization and Reprocessing (EMDR), a much publicized but controversial treatment, integrates components of exposure and cognitive therapies with therapist-directed eye movements.^28-30 Patients imagine their trauma while the therapist directs their eye movements, which is thought to provide exposure to trauma images and memories, thereby reducing symptoms. EMDR has been found to reduce PTSD symptoms with a low to moderate strength-of-evidence rating.²⁶ However, it has not proved more effective than other exposure and cognitive therapies, and its unique component (eg, eye movements) has not added any effect to outcomes.^28-31

Other newer therapies, such as Acceptance and Commitment Therapy^7,24,27 and online and computer-assisted treatments, are being evaluated.¹⁴

Medications take on an adjunct role to therapy

Drug treatment of PTSD has not been effective in children or adolescents.^4,8 In adults, medications have helped relieve some symptoms of PTSD. However, given their low effect sizes, medications are not recommended as first-line treatments over exposure and TF-CBT. Their usefulness lies chiefly in an adjunct role to exposure and cognitive therapies or for patients who refuse psychotherapy.^4,8,25

Selective serotonin reuptake inhibitors such as fluoxetine, paroxetine, and sertraline, have been effective for such PTSD symptoms as intrusive thoughts, negative or irritable mood, anxiety, restlessness, attention difficulties, and hyperarousal.^1,8

While benzodiazepines have been used to control anxiety, hyperarousal, and insomnia, they have not been effective for most other PTSD symptoms, including avoidance, re-experiencing, and cognitive symptoms. Furthermore, they are not recommended given their augmentative effect on other related symptoms and associated conditions (eg, dissociation, disinhibition, substance abuse) and possible interference with desensitization that occurs in exposure therapy.^1,5

While PTSD is detected more often among veterans, due to regular screening through the VA system, most cases are related to civilian traumas, such as sexual assault.

If a patient has significant insomnia and PTSD-related nightmares, consider starting prazosin at 1 mg/d and titrating up to an effective dose, which typically ranges from 5 to 20 mg per day.^1,5 Additionally, trazodone or antihistamines may be used to enhance sleep.¹

COORDINATION OF CARE

Upon identifying PTSD and offering treatment, introduce the patient to a mental health provider as part of the referral process, which strongly encourages patient engagement in treatment.¹⁴ Collaborate with the psychotherapist throughout treatment to facilitate a biopsychosocial approach to the patient’s care, and coordinate the monitoring and treatment of any comorbid physical conditions.

The Substance Abuse and Mental Health Services Administration has proposed a framework for multisystem Trauma-Informed Care (TIC), in which the primary care physician has many roles, including:^12,20

• recording or communicating sensitive private information to other providers through the electronic medical record in a manner that does not interfere with a patient’s development of trust or lead to exposure and retraumatization,
• performing invasive physical exams in a sensitive and patient-centered manner, and
• using support and shared decision-making in clinical encounters.

Physicians can also connect patients with PTSD to programs or groups that aid in developing resilience, such as physical exercise classes, social support networks, and community involvement opportunities.⁴

CASE

The physician referred Mr. W to an onsite psychologist. At a subsequent clinic visit in which he was seen by a different primary care physician, Mr. W expressed new concerns about shoulder pain and changes in a mole. During this visit, Mr. W was asked whether he had followed up on the earlier referral for counseling. He replied that he had attended an intake appointment with the psychologist, but that he had not wanted to talk about what had happened to him and therefore avoided future appointments.*

He remained concerned that he might have an STD, but declined medication for PTSD because he felt he was “moving on” with his life.

*Author’s note: Getting patients to open up about their trauma exposure can be difficult. If the patient isn’t ready, simply bringing up the experience can trigger avoidance. It’s often helpful to encourage patients to first develop a relationship with their therapist, then later discuss the details of their trauma when they are ready. This encourages patients to engage in the counseling process.

CORRESPONDENCE
Adrienne A. Williams, PhD, Department of Family Medicine, University of Illinois at Chicago College of Medicine, 1919 W Taylor Street, MC663, Chicago, IL 60612; [email protected].

THE CASE

DeSean W,* a 47-year-old man, returned to his primary care clinic with a new complaint of epigastric burning that had been bothering him for the past 4 months. He had tried several over-the-counter remedies, which provided no relief. He also remained concerned—despite assurances to the contrary at previous clinic visits—that he had contracted a sexually-transmitted disease (STD) after going to a bar one night 4 to 5 months ago. At 2 other clinic visits since that time, STD test results were negative. At this current visit, symptoms and details of sexual history were unchanged since the last visit, with the exception of the epigastric pain.

When asked if he thought he had contracted an STD through a sexual encounter the night he went to the bar, he emphatically said he would not cheat on his wife. Surprisingly, given his concern, he avoided further discussion on modes of contracting an STD.

The physician prescribed ranitidine 150 mg bid for the epigastric burning and explained, once more, the significance of the STD test results. However, he also decided to further examine Mr. W’s concern about STDs and the night he may have contracted one.

HOW WOULD YOU PROCEED WITH THIS PATIENT?

*The patient’s name has been changed to protect his privacy.

SCOPE OF THE PROBLEM

Despite being as common as asthma, posttraumatic stress disorder (PTSD) often remains undiagnosed and untreated in primary care.¹ In brief, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines PTSD as persistent and long-term changes in thoughts or mood following actual or threatened exposure to death, serious injury, or sexual assault that leads to re-experiencing, functional impairment, physiologic stress reactions, and avoidance of thoughts or situations associated with the original trauma.² More than one in 10 women and one in 20 men experience PTSD in their lifetime.^2,3 Population-based studies have not yet determined the prevalence among children.³ Almost 40% of US adults report having experienced a trauma before age 13, and about one-third of these go on to develop PTSD.⁴

Individuals with PTSD have higher rates of somatic complaints, overall medical utilization, prescription use, physical and social disability, attempted suicide, and all-cause mortality.^3,5-7 PTSD is associated with increased risk for cardiac, gastrointestinal, metabolic, and immunologic illnesses, other psychiatric illnesses, risky health behaviors, and decreased medical adherence.^4,6 Additionally, prevention and treatment efforts for STDs and obesity are less effective among those with trauma histories.⁴ Thus, detection and treatment of PTSD improves the likelihood of successfully treating other health concerns.

THE ESSENTIALS OF A PTSD DIAGNOSIS

DSM-5 diagnosis of PTSD requires the experience of a trauma and resultant symptoms from each of 4 symptom-clusters:²

• one or more re-experiencing symptoms (eg, intrusive memories or recurrent distressing dreams, psychological distress or physiologic reactions to reminders of the trauma)
• one or more avoidance symptoms (eg, avoidance of trauma memories or of people and places that trigger a reminder of the trauma)
• two or more changes in thoughts or mood (eg, negative beliefs about self or others, social detachment, anhedonia)
• two or more changes in arousal activity (eg, sleep problems, hypervigilance, inability to concentrate).

Since many people experiencing traumas do not develop PTSD,^5,8 symptoms must last at least one month to meet the criteria for diagnosis.² Sexual trauma, experiencing multiple traumas, and lack of social support increase the risk that an individual will develop PTSD.^9-11 Notably, symptom onset will be delayed 6 months or more in some individuals,^2,8 making it more difficult for those patients and clinicians to connect symptoms to the trauma.¹²

Differential diagnosis

PTSD must be differentiated from other mental health conditions with overlapping symptoms (TABLE 1^2,8,13), but it may also be comorbid with one or more of these other conditions. When patients with PTSD do report mental health symptoms, providers often focus on the depressive symptoms that overlap with PTSD, and on substance use, which often accompanies PTSD, leaving PTSD undetected.⁹

Given that depressed/irritable mood, decreased participation in pleasurable activities, negative views of the world, attention difficulties, sleep difficulties, feelings of guilt, and agitation/restlessness are symptoms of both depression and PTSD,² it is particularly important to screen patients with depressive symptoms for trauma history.

Why PTSD is often missed

Due to the impact of PTSD on overall health, the rates of PTSD in primary care clinics may be higher than in the general population.¹⁴ Thus, primary care clinicians are likely seeing PTSD more often than they realize. In fact, a systematic review showed that clinicians detected 0% to 52% of their patients with PTSD, missing at least half of all PTSD diagnoses.⁹

Prevention and treatment efforts for STDs and obesity are less effective among those with trauma histories.

Detecting PTSD can be challenging for several reasons. Symptoms can span the emotional, social, physical, and behavioral aspects of an individual’s life, so patients and clinicians alike may regard symptoms as unrelated to PTSD.⁸ Primary symptom presentation may vary, with some people reporting anxiety symptoms, others mostly depressive symptoms, and others arousal, dissociative, or—as in our patient’s case—somatic symptoms.² In affected children, parents may report emotional or behavioral problems without mentioning the trauma.² Additionally, for traumas that were not a single event, such as long-term child abuse, patients may have difficulty identifying symptom onset.²

CASE

The physician screened Mr. W for trauma exposure as part of the differential. Mr. W revealed that he had blacked out at the bar, despite drinking only moderately, and that he awoke with anal pain. He believed he had been drugged and sexually assaulted. Further screening for PTSD symptoms related to this event confirmed multiple associated symptoms. He acknowledged that his epigastric pain had started soon after the trauma and, after further discussion, began to link his stomach pain and other new symptoms revealed by the PTSD screen (hypervigilance, avoidance, change in mood) to the trauma.

As happened in this case, most PTSD patients present with somatic complaints rather than reporting a traumatic experience and having associated effects. This in turn usually leads clinicians to consider only non-PTSD diagnoses.^6,9,15 Core avoidance symptoms are a major reason for such a presentation in PTSD patients.¹⁴ Patients avoid thoughts, feelings, and conversations that remind them of the trauma.¹³ As a result, they are less likely to voluntarily report trauma. They avoid thinking about how their current symptoms may be associated with their trauma and are reluctant to talk about their trauma with clinicians.^5,9,8,12

Another barrier to diagnosis is a belief that PTSD is primarily experienced by combat veterans¹ (TABLE 2^{2,4-6,8,9,12,14-18}). While PTSD is detected more often among veterans due to regular screening through the Department of Veterans Affairs,¹⁴ the vast majority of PTSD cases are related to civilian traumas such as sexual assault, child abuse, and car accidents.^5,9 In fact, the estimated 9% prevalence¹⁶ of PTSD among the 18.8 million US veterans¹⁷ (1.7 million veterans with PTSD) accounts for less than 10% of the total lifetime prevalence² of PTSD in the US population (27.9 million people with PTSD).¹⁸


SCREENING: WHAT TO LOOK FOR

Since individuals with PTSD mainly seek treatment for associated physical symptoms,¹⁴ primary care is particularly important for identification of PTSD and treatment access. The US Preventative Services Task Force does not yet have any recommendations for screening for PTSD. The American Psychiatric Association recommends that a trauma history be included in all initial psychiatric evaluations of adults.¹⁹ Screens can target high-risk populations and can be repeated across the lifespan,⁹ as traumas can occur at any age and symptoms may not emerge until years after the trauma.^2,4 Factors in a patient’s history associated with high risk of PTSD include the following:

• known trauma exposure (eg, treatment at the emergency department following motor vehicle collision, natural disaster, assault),⁶
• frequent medical visits or unexplained physical symptoms,^5,8
• family members who are trauma victims,⁸
• involvement in juvenile justice system,^4,12
• sensitive or invasive exams (eg, pelvic exams) that trigger symptoms or contribute to retraumatization,^12,20 and
• any medical condition (eg, hypertension, chronic pain, sleep disorder), self-destructive behavior (eg, drug or alcohol abuse, low impulse control), or social/occupational issues (eg, unemployment, social isolation, fighting) with a known link to PTSD.^2,4,6,8

The first step in screening. Given a patient’s reported symptoms, assess for trauma exposure to determine whether PTSD should be included in the differential diagnosis. Overlooking PTSD as a possible source of symptoms can result in misattributing them to other causes.^4,8 Listing common traumas, or using a standardized list such as the Life Events Checklist, can help identify patients with trauma exposure.^8,21 However, do not make the patient provide details of the traumatic event(s), as that can exacerbate symptoms if PTSD is present.⁶ It is sufficient to know the category of the trauma (eg, sexual assault) without making the patient describe who was involved and what happened.⁶

The second step in screening. If a patient reveals trauma exposure, consider using an instrument such as the Primary Care PTSD Screen (PC-PTSD) or the PTSD Checklist, both available online, to screen for PTSD symptoms related to the identified trauma.^6,9,21-23 Since these measures screen for symptoms but do not ask about trauma exposure, false positives can occur if a trauma is not first identified (such as through the Life Events Checklist) due to symptom overlap with other conditions (TABLE 1^2,8,13).²¹

Treatment is effective, even decades after a traumatic event

Provide anyone who has been traumatized with information about common after effects, symptoms of PTSD, and available treatments.⁸ Keep in mind that initial symptom severity after trauma exposure does not correlate with long-term symptoms,⁸ and about half of adults will recover without treatment within 3 months.^1,2,5 The first month of symptoms may be addressed with patient education and watchful waiting. But if symptoms don’t subside after a month, consider offering treatment¹ with the understanding that, for some individuals, symptoms may yet resolve on their own.

Detecting and treating PTSD early can decrease its deleterious effects on health and cut down on years of functional impairment.¹ Even decades after an initial traumatic event, PTSD treatments can be effective.⁸ Children may experience functional impairment without meeting full criteria for PTSD, and can also benefit from treatment.⁷

INTEGRATING EXPOSURE AND COGNITIVE THERAPIES IS KEY

Offer any patient who meets criteria for PTSD a referral for exposure therapy and trauma-focused cognitive behavioral therapy (TF-CBT), the first-line treatments for PTSD.^1,4,8,24,25

Exposure therapies for PTSD are supported by strong evidence and help patients to become desensitized to distressful memories through gradual, repeated exposures in a relaxed or safe space.^8,26

Cognitive methods, such as cognitive processing therapy, cognitive behavioral therapy, and cognitive reprocessing have moderate strength of evidence, and may be combined with exposure therapy.²⁶ Cognitive therapies help patients change thoughts, beliefs, and behaviors that contribute to PTSD symptoms.^8,26

Exposure and TF-CBT have the most empirical evidence for child, adolescent, and adult PTSD, and are effective for the range of PTSD symptoms,^4,8,25 including avoidance—a fundamental component of PTSD that drives other PTSD symptoms²⁷—comorbid depression, and other emotions associated with trauma (eg, shame, guilt, and anger).^8,25 Family involvement is recommended for children and adolescents.⁴

Screen for a history of trauma in any patient who has depressive symptoms.

For patients with comorbid substance abuse, offer integrated PTSD/substance abuse treatment, which is more effective than isolated treatment of each.⁴ Relaxation training can be helpful as an adjunct to TF-CBT, but is not sufficient as a stand-alone treatment.¹³ Other psychotherapies, such as supportive, psychodynamic, systemic, and hypnotherapy, have not proved effective.¹⁴

Eye Movement Desensitization and Reprocessing (EMDR), a much publicized but controversial treatment, integrates components of exposure and cognitive therapies with therapist-directed eye movements.^28-30 Patients imagine their trauma while the therapist directs their eye movements, which is thought to provide exposure to trauma images and memories, thereby reducing symptoms. EMDR has been found to reduce PTSD symptoms with a low to moderate strength-of-evidence rating.²⁶ However, it has not proved more effective than other exposure and cognitive therapies, and its unique component (eg, eye movements) has not added any effect to outcomes.^28-31

Other newer therapies, such as Acceptance and Commitment Therapy^7,24,27 and online and computer-assisted treatments, are being evaluated.¹⁴