Case Reports

The number of veterans aged ≥ 65 years is expected to increase steadily as the Vietnam-era cohort ages. In 2012, the number of veterans aged ≥ 85 years was expected to peak at nearly 1.4 million. Vietnam-era veterans comprise the largest cohort of veterans, and > 15% of male and > 8% of female Vietnam veterans receiving care in the VA system have been diagnosed with posttraumatic stress disorder (PTSD). These veterans are rapidly approaching age groups in which cognitive disorders increase exponentially in prevalence.

Combat exposure has been called a common but “hidden variable” in studies of aging and health.¹ Combat exposure may be even more hidden for Vietnam veterans who have pursued health care outside the VA system and less likely to announce their service to health care providers.

Even veterans who did not serve in traditional combat roles can experience chronic debilitation from the psychological stress of overseas deployment to a war zone. Indeed, cases of noncombat trauma have been presented in the context of cognitive decline and late-onset PTSD.² It is probable that survivors of sexual assault, child abuse, crime, and natural disaster are also vulnerable to a recurrence of trauma symptoms if they experience cognitive slippage. In this article the authors report a case of delayed onset PTSD symptoms, precipitated by cognitive decline.

Case Report

Mr. B was a 72-year-old Korean War veteran referred for neuropsychological evaluation to establish baseline cognitive status before elective cardiac surgery. Mr. B relied on his wife to fill in many details of his personal history. His wife reported that the patient’s memory problems had increased significantly over the previous 12 months. Mr. B had been treated with donepezil 10 mg daily for about 1 year, with no observed benefit. His wife described life at home as “tense” due to his increased irritability and poor insight into his condition. Mr. B reported that he was often afraid of noises at night and needed to go outside and look around. His wife reported that he was very afraid of “strangers coming into the house.”

Mr. B was born in Arizona and experienced significant physical abuse while under the care of an alcoholic foster parent. He dropped out of high school and enlisted in the U.S. Marine Corps. Upon his discharge from military service, he worked as a truck driver for 23 years. He retired after experiencing hip problems. He drank heavily for many years after the war and, according to his wife, was “very violent,” but stopped 27 years previously, after injuring his wife while intoxicated. The patient’s medical history included hospitalization about 1 year prior to the evaluation following a fall associated with altered level of consciousness and confusion, which lasted several hours. He was discharged the same day and was thought to have had a stroke. The patient also had hypertension, hyperlipidemia, and sciatica. A carotid ultrasound showed bilateral carotid stenosis > 50%.

Mr. B was married for 45 years and had 5 children and 12 grandchildren. He enlisted in the U.S. Marine Corps at age 19 and served as a tank gunner during the Korean War. He experienced extremely heavy combat, was wounded several times (including loss of consciousness due to an explosion), and was hospitalizedfor 4 m onths in Japan. When he returned to the frontline, he found that many of the men in his unit had been killed. He was promoted to staff sergeant and tank commander. Mr. B received an honorable discharge after the war and a 50% service-connected disability pension for PTSD. He reported having received group psychotherapy at a VA hospital soon after the war but no other psychiatric treatment. He avoided watching the news because the Gulf War news reminded him of Korea.

Mr. B was smiling, pleasant, and cooperative throughout the 2 hours of testing and interviewing. He wore a Korean War veteran baseball cap festooned with military pins and ribbons, including a Purple Heart ribbon that he proudly showed to the test administrators. Unbidden, he also presented for inspection an assortment of life membership cards in various veterans service organizations. Mr. B reported frequent nightmares, night sweats, and intrusive thoughts about his combat experiences. During testing, he was repeatedly triggered by innocuous items and launched into a discourse on his combat experiences. When asked to memorize a short list of words that included the word fire, he said, “You know what that reminds me of...we had to fire big guns, 90 millimeter, that’s what it was…killing and how to kill.” When shown an abstract design that resembled the number 44, he said, “You know what that is? It was the radio call sign of our tank—‘This is 44, come in, we need some help.’”

Mr. B’s memory problems were marked by rapid forgetting, impaired ability to learn new information, and impaired ability to recall previously learned information. Language problems were also present, including difficulty recognizing and naming common objects, impaired auditory comprehension, and problems with verbal associative fluency during timed tasks. He also showed difficulties with executive functioning, attention, and working memory. His mini-mental state examination score was 21/30. He stated the year was 2020, did not know the day of the week, registered 2/3 words and recalled 0/3, he counted 3/5 in serial 7s, and was unable to repeat the phrase, “no ifs, ands, or buts.”

Discussion

Posttraumatic stress symptoms were present during the immediate aftermath of the initial trauma exposure for this patient. He managed to lead a relatively successful and productive life, sustained a marriage, and raised a family. The onset of cognitive decline precipitated a recrudescence of PTSD symptomology. In fact, the effects of combat trauma seem more malignant and extreme at the time of the memory disorders evaluation than at any prior time in his life.

A number of case reports have been published in recent years that describe comorbid presentations of cognitive disorder and PTSD symptomatology.^3-6 A clinicalconsensus that cognitive decline can exacerbate previously well-managed symptoms of earlier psychological trauma seems to be emerging. Several published casestudies have noted that comorbid presentation of dementia and PTSD is often marked by violence, psychotic symptoms, and increased risk of hospitalization.^7-9

PTSD Research

Unfortunately, systematic investigation into the relationship between PTSD and cognitive decline is in its infancy. Previous authors have posited various mechanisms to explain the exacerbation of dormant PTSD symptoms after cognitive decline.^10,11 Some have attributed the phenomenon to an age-related failure of either repression or avoidance or to a compromised ability to actively focus their attention elsewhere.^2,12 A finding of preservative errors on neuropsychological tests has been associated with an inability to organize and inhibit intrusive thought.¹³ In one case, the effects of combat trauma were purported to be denied, repressed, and largely forgotten for 30 years until rekindled by the patient’s deteriorating health and loss of employment.¹⁴ Several case examples have been presented in which physical illness, interpersonal loss, retirement, or losses of social support were other factors.^15-18 Two major studies of veterans with PTSD, found that subjects were twice as likely to develop dementia.^3,4 There is a strong association between chronic psychological stress and later development
of dementia. In a study by Wilson and colleagues, subjects with higher baseline stress had twice the chance of developing Alzheimer disease.19 Similar findings of
accelerated or higher cognitive decline were found by other studies, too.^17,20

Hippocampal damage associated with prolonged, intense psychological stress has been cited as a possible contributor to PTSD symptom recrudescence in older adults.²¹ It is well known that emotional arousal leads to better-encoded memories. In the context of a cognitive disorder marked by gradual memory loss, traumatic memories might be the last to go.²² Another proposed biologic mechanism is a reduction in hippocampal volume and decreased inhibition of the amgydala, which results in preferential recall of the nondeclarative, amygdaloidal traumatic memories.⁸

Research on selective area damage in the hippocampus opens a new era of understanding of consequences of stress. The dentate gyrus (DG) is the main area of hippocampus that helps in neurogenesis and cornus ammonis 3 (CA3) for dendritic branching.^23-25 In recent studies by Wang and colleagues, PTSD has been found to be associated with selective volume loss of the CA3/DG subfields, consistent with animal studies.^24-28 Abundance of glucocorticoid receptors in the hippocampus, especially at CA3^,29,30 may make it more vulnerable to the neurotoxic effect of glucocorticoids, causing suppression of neurogenesis,²⁹ diminished dendritic branching,30 loss of synapses,^26,31 and eventually diminished neuroplasticity,32 because CA3/DG is the main target of neurotoxicity by glucocorticoid and inflammatory damage.

The results of neuroimaging studies suggest that decreased integration of the prefrontal cortex and the hippocampus results in impaired short-term memory and perhaps increasing the prominence of long-term distressing memories.³³ Clinical observation confirms that patients with PTSD experience vivid, intense, detailed, and realistic recollections of remote memories at a time when their ability to recall nontraumatic autobiographical detail is severely compromised.

Symptom Reemergence

Both prospective and retrospective studies have shown that PTSD symptoms can evolve, even after a 20-year long symptom-free period, and reemergence of PTSD
symptoms is not uncommon.^34,35 A longer delay usually presents with less severe symptoms.³⁶ The unavailability of complete information regarding a patient’s past adjustment to psychological trauma has encouraged some experts to label exacerbation of PTSD symptoms precipitated by cognitive disorder as delayed onset PTSD. In most cases, it seems that this is more accurately described as a recrudescence of symptoms that were better managed previously. The picture is clouded by the often bizarre and extreme manifestation of PTSD symptoms in patients with memory disorders. The course of PTSD often does involve a delay between the time of exposure to trauma and symptom manifestation. In addition, symptom intensity can fluctuate significantly over the course of this often chronic illness.

The suffering associated with PTSD is often personal and concealed. Family and other collateral sources may be able to report only on social and occupational functioning. The authors recommend increased attention to proper assessment of (1) remote trauma history in patients being evaluated for memory disorders; and (2) cognitive decline in patients with history of PTSD. The problem of underreported cognitive decline is well known, although its extent is not. Early detection may help to mitigate the combined effects of these conditions. Aggressive early treatment of symptoms during the onset of cognitive dysfunction may prolong patients’ ability to remain at home.

Patient Care

Mr. B’s case was marked by significant tension in the home. Education and support of caregivers is essential to maintaining care in the least restrictive setting, such as the patient’s home. Families might be utterly bewildered by a patient’s apparently sudden preoccupation with traumatic memories. For many, this might be the first time they have ever heard the patient speak at length about the traumatic events. Simple strategies to limit exposure to distressing stimuli, improve grounding, and understand the effects of trauma can be taught. Psychopharmacologic intervention to improve sleep, slow cognitive decline, and decrease behavioral disturbances may be indicated.

Behavioral disturbance is frequently encountered when treating patients with cognitive impairment. In the limited literature on the subject, patients with both PTSD and cognitive impairment do not seem to be more prone to behavioral disturbance than patients with cognitive impairment alone.⁹ However, the case reports cited here demonstrate a high incidence of violence or potential violence in these comorbid patients. Routine assessment of potential harm from firearms or other weapons should be conducted assiduously.

It is possible that Vietnam War veterans may be more likely than previous veterans to exhibit behavioral disturbances in the context of cognitive decline and PTSD. A higher incidence of aggression, violence, and resistance to authority has been documented in this group.³⁷ Substance abuse and dependence also occurs with higher frequency in this cohort and may complicate treatment of cognitive impairment and PTSD.^38,39 A large number of these veterans may initially present to non-VA health care providers and these clinicians may be unaware of a patient’s prior combat exposure and thus fail to accurately assess PTSD.

Although the relation of PTSD and vulnerability to dementia has been well established, it is unknown how the presence of PTSD symptomatology impacts dementia symptoms or how the presence of dementia impacts PTSD symptoms. Posttraumatic stress disorder and dementia share similar risks like traumatic brain injury, low IQ, poor education, substance abuse, precipitated by stressful life events and impairment of coping, physical health and related risk factors. Unmasking PTSD symptoms resulting from dementia is a well-known phenomenon described in recent studies on late-onset stress symptomatology (LOSS).^5,10,40

Since PTSD is a major risk factor that doubles the chance of developing dementia, mandatory screening for dementia in older patients along with assessment of other risk factors as a standard of care may help physicians in the early detection and initiation of care. Recognition of LOSS may be an important milestone in the treatment of delayed onset PTSD, which is considered a normal aging process and a premorbid stage of PTSD.^10,40

Although there is no established treatment, early psychotherapeutic approaches like reminiscent therapy along with psychoeducation may be beneficial in patients with LOSS.^40-42 Effective treatments for PTSD with patients with dementia may be challenging, though dementia was not found to be a barrier to implement prolonged exposure therapy in patients with mild cognitive impairment.43 Patient aligned care teams can be an ideal approach for the care of these veterans.

Conclusion

Posttraumatic stress disorder and dementia are well studied and documented disorders, although PTSD has been studied far more extensively in younger populations. Accounts of comorbidity of the 2 disorders are limited in the literature. Individuals may exhibit PTSD symptoms prior to the onset of dementia. They also may develop or uncover long quiescent symptoms of the disease. The populations of patients with PTSD and dementia are recognized, but their characteristics are largely unstudied and thus unknown.

Although the authors believe this to be a phenomenon of unrecognized coexistence of the 2 disorders, a disproportionate number of patients may be found in certain populations, especially among veterans. There is good evidence to expect increased numbers of these patients in the VA system, especially given the relative frequency of PTSD symptoms in aging cohorts of VA patients.

Click here to continue reading.

The number of veterans aged ≥ 65 years is expected to increase steadily as the Vietnam-era cohort ages. In 2012, the number of veterans aged ≥ 85 years was expected to peak at nearly 1.4 million. Vietnam-era veterans comprise the largest cohort of veterans, and > 15% of male and > 8% of female Vietnam veterans receiving care in the VA system have been diagnosed with posttraumatic stress disorder (PTSD). These veterans are rapidly approaching age groups in which cognitive disorders increase exponentially in prevalence.

Combat exposure has been called a common but “hidden variable” in studies of aging and health.¹ Combat exposure may be even more hidden for Vietnam veterans who have pursued health care outside the VA system and less likely to announce their service to health care providers.

Even veterans who did not serve in traditional combat roles can experience chronic debilitation from the psychological stress of overseas deployment to a war zone. Indeed, cases of noncombat trauma have been presented in the context of cognitive decline and late-onset PTSD.² It is probable that survivors of sexual assault, child abuse, crime, and natural disaster are also vulnerable to a recurrence of trauma symptoms if they experience cognitive slippage. In this article the authors report a case of delayed onset PTSD symptoms, precipitated by cognitive decline.

Case Report

Mr. B was a 72-year-old Korean War veteran referred for neuropsychological evaluation to establish baseline cognitive status before elective cardiac surgery. Mr. B relied on his wife to fill in many details of his personal history. His wife reported that the patient’s memory problems had increased significantly over the previous 12 months. Mr. B had been treated with donepezil 10 mg daily for about 1 year, with no observed benefit. His wife described life at home as “tense” due to his increased irritability and poor insight into his condition. Mr. B reported that he was often afraid of noises at night and needed to go outside and look around. His wife reported that he was very afraid of “strangers coming into the house.”

Mr. B was born in Arizona and experienced significant physical abuse while under the care of an alcoholic foster parent. He dropped out of high school and enlisted in the U.S. Marine Corps. Upon his discharge from military service, he worked as a truck driver for 23 years. He retired after experiencing hip problems. He drank heavily for many years after the war and, according to his wife, was “very violent,” but stopped 27 years previously, after injuring his wife while intoxicated. The patient’s medical history included hospitalization about 1 year prior to the evaluation following a fall associated with altered level of consciousness and confusion, which lasted several hours. He was discharged the same day and was thought to have had a stroke. The patient also had hypertension, hyperlipidemia, and sciatica. A carotid ultrasound showed bilateral carotid stenosis > 50%.

Mr. B was married for 45 years and had 5 children and 12 grandchildren. He enlisted in the U.S. Marine Corps at age 19 and served as a tank gunner during the Korean War. He experienced extremely heavy combat, was wounded several times (including loss of consciousness due to an explosion), and was hospitalizedfor 4 m onths in Japan. When he returned to the frontline, he found that many of the men in his unit had been killed. He was promoted to staff sergeant and tank commander. Mr. B received an honorable discharge after the war and a 50% service-connected disability pension for PTSD. He reported having received group psychotherapy at a VA hospital soon after the war but no other psychiatric treatment. He avoided watching the news because the Gulf War news reminded him of Korea.

Mr. B was smiling, pleasant, and cooperative throughout the 2 hours of testing and interviewing. He wore a Korean War veteran baseball cap festooned with military pins and ribbons, including a Purple Heart ribbon that he proudly showed to the test administrators. Unbidden, he also presented for inspection an assortment of life membership cards in various veterans service organizations. Mr. B reported frequent nightmares, night sweats, and intrusive thoughts about his combat experiences. During testing, he was repeatedly triggered by innocuous items and launched into a discourse on his combat experiences. When asked to memorize a short list of words that included the word fire, he said, “You know what that reminds me of...we had to fire big guns, 90 millimeter, that’s what it was…killing and how to kill.” When shown an abstract design that resembled the number 44, he said, “You know what that is? It was the radio call sign of our tank—‘This is 44, come in, we need some help.’”

Mr. B’s memory problems were marked by rapid forgetting, impaired ability to learn new information, and impaired ability to recall previously learned information. Language problems were also present, including difficulty recognizing and naming common objects, impaired auditory comprehension, and problems with verbal associative fluency during timed tasks. He also showed difficulties with executive functioning, attention, and working memory. His mini-mental state examination score was 21/30. He stated the year was 2020, did not know the day of the week, registered 2/3 words and recalled 0/3, he counted 3/5 in serial 7s, and was unable to repeat the phrase, “no ifs, ands, or buts.”

Discussion

Posttraumatic stress symptoms were present during the immediate aftermath of the initial trauma exposure for this patient. He managed to lead a relatively successful and productive life, sustained a marriage, and raised a family. The onset of cognitive decline precipitated a recrudescence of PTSD symptomology. In fact, the effects of combat trauma seem more malignant and extreme at the time of the memory disorders evaluation than at any prior time in his life.

A number of case reports have been published in recent years that describe comorbid presentations of cognitive disorder and PTSD symptomatology.^3-6 A clinicalconsensus that cognitive decline can exacerbate previously well-managed symptoms of earlier psychological trauma seems to be emerging. Several published casestudies have noted that comorbid presentation of dementia and PTSD is often marked by violence, psychotic symptoms, and increased risk of hospitalization.^7-9

PTSD Research

Unfortunately, systematic investigation into the relationship between PTSD and cognitive decline is in its infancy. Previous authors have posited various mechanisms to explain the exacerbation of dormant PTSD symptoms after cognitive decline.^10,11 Some have attributed the phenomenon to an age-related failure of either repression or avoidance or to a compromised ability to actively focus their attention elsewhere.^2,12 A finding of preservative errors on neuropsychological tests has been associated with an inability to organize and inhibit intrusive thought.¹³ In one case, the effects of combat trauma were purported to be denied, repressed, and largely forgotten for 30 years until rekindled by the patient’s deteriorating health and loss of employment.¹⁴ Several case examples have been presented in which physical illness, interpersonal loss, retirement, or losses of social support were other factors.^15-18 Two major studies of veterans with PTSD, found that subjects were twice as likely to develop dementia.^3,4 There is a strong association between chronic psychological stress and later development
of dementia. In a study by Wilson and colleagues, subjects with higher baseline stress had twice the chance of developing Alzheimer disease.19 Similar findings of
accelerated or higher cognitive decline were found by other studies, too.^17,20

Hippocampal damage associated with prolonged, intense psychological stress has been cited as a possible contributor to PTSD symptom recrudescence in older adults.²¹ It is well known that emotional arousal leads to better-encoded memories. In the context of a cognitive disorder marked by gradual memory loss, traumatic memories might be the last to go.²² Another proposed biologic mechanism is a reduction in hippocampal volume and decreased inhibition of the amgydala, which results in preferential recall of the nondeclarative, amygdaloidal traumatic memories.⁸

Research on selective area damage in the hippocampus opens a new era of understanding of consequences of stress. The dentate gyrus (DG) is the main area of hippocampus that helps in neurogenesis and cornus ammonis 3 (CA3) for dendritic branching.^23-25 In recent studies by Wang and colleagues, PTSD has been found to be associated with selective volume loss of the CA3/DG subfields, consistent with animal studies.^24-28 Abundance of glucocorticoid receptors in the hippocampus, especially at CA3^,29,30 may make it more vulnerable to the neurotoxic effect of glucocorticoids, causing suppression of neurogenesis,²⁹ diminished dendritic branching,30 loss of synapses,^26,31 and eventually diminished neuroplasticity,32 because CA3/DG is the main target of neurotoxicity by glucocorticoid and inflammatory damage.

The results of neuroimaging studies suggest that decreased integration of the prefrontal cortex and the hippocampus results in impaired short-term memory and perhaps increasing the prominence of long-term distressing memories.³³ Clinical observation confirms that patients with PTSD experience vivid, intense, detailed, and realistic recollections of remote memories at a time when their ability to recall nontraumatic autobiographical detail is severely compromised.

Symptom Reemergence

Both prospective and retrospective studies have shown that PTSD symptoms can evolve, even after a 20-year long symptom-free period, and reemergence of PTSD
symptoms is not uncommon.^34,35 A longer delay usually presents with less severe symptoms.³⁶ The unavailability of complete information regarding a patient’s past adjustment to psychological trauma has encouraged some experts to label exacerbation of PTSD symptoms precipitated by cognitive disorder as delayed onset PTSD. In most cases, it seems that this is more accurately described as a recrudescence of symptoms that were better managed previously. The picture is clouded by the often bizarre and extreme manifestation of PTSD symptoms in patients with memory disorders. The course of PTSD often does involve a delay between the time of exposure to trauma and symptom manifestation. In addition, symptom intensity can fluctuate significantly over the course of this often chronic illness.

The suffering associated with PTSD is often personal and concealed. Family and other collateral sources may be able to report only on social and occupational functioning. The authors recommend increased attention to proper assessment of (1) remote trauma history in patients being evaluated for memory disorders; and (2) cognitive decline in patients with history of PTSD. The problem of underreported cognitive decline is well known, although its extent is not. Early detection may help to mitigate the combined effects of these conditions. Aggressive early treatment of symptoms during the onset of cognitive dysfunction may prolong patients’ ability to remain at home.

Patient Care

Mr. B’s case was marked by significant tension in the home. Education and support of caregivers is essential to maintaining care in the least restrictive setting, such as the patient’s home. Families might be utterly bewildered by a patient’s apparently sudden preoccupation with traumatic memories. For many, this might be the first time they have ever heard the patient speak at length about the traumatic events. Simple strategies to limit exposure to distressing stimuli, improve grounding, and understand the effects of trauma can be taught. Psychopharmacologic intervention to improve sleep, slow cognitive decline, and decrease behavioral disturbances may be indicated.

Behavioral disturbance is frequently encountered when treating patients with cognitive impairment. In the limited literature on the subject, patients with both PTSD and cognitive impairment do not seem to be more prone to behavioral disturbance than patients with cognitive impairment alone.⁹ However, the case reports cited here demonstrate a high incidence of violence or potential violence in these comorbid patients. Routine assessment of potential harm from firearms or other weapons should be conducted assiduously.

It is possible that Vietnam War veterans may be more likely than previous veterans to exhibit behavioral disturbances in the context of cognitive decline and PTSD. A higher incidence of aggression, violence, and resistance to authority has been documented in this group.³⁷ Substance abuse and dependence also occurs with higher frequency in this cohort and may complicate treatment of cognitive impairment and PTSD.^38,39 A large number of these veterans may initially present to non-VA health care providers and these clinicians may be unaware of a patient’s prior combat exposure and thus fail to accurately assess PTSD.

Although the relation of PTSD and vulnerability to dementia has been well established, it is unknown how the presence of PTSD symptomatology impacts dementia symptoms or how the presence of dementia impacts PTSD symptoms. Posttraumatic stress disorder and dementia share similar risks like traumatic brain injury, low IQ, poor education, substance abuse, precipitated by stressful life events and impairment of coping, physical health and related risk factors. Unmasking PTSD symptoms resulting from dementia is a well-known phenomenon described in recent studies on late-onset stress symptomatology (LOSS).^5,10,40

Since PTSD is a major risk factor that doubles the chance of developing dementia, mandatory screening for dementia in older patients along with assessment of other risk factors as a standard of care may help physicians in the early detection and initiation of care. Recognition of LOSS may be an important milestone in the treatment of delayed onset PTSD, which is considered a normal aging process and a premorbid stage of PTSD.^10,40

Although there is no established treatment, early psychotherapeutic approaches like reminiscent therapy along with psychoeducation may be beneficial in patients with LOSS.^40-42 Effective treatments for PTSD with patients with dementia may be challenging, though dementia was not found to be a barrier to implement prolonged exposure therapy in patients with mild cognitive impairment.43 Patient aligned care teams can be an ideal approach for the care of these veterans.

Conclusion

Posttraumatic stress disorder and dementia are well studied and documented disorders, although PTSD has been studied far more extensively in younger populations. Accounts of comorbidity of the 2 disorders are limited in the literature. Individuals may exhibit PTSD symptoms prior to the onset of dementia. They also may develop or uncover long quiescent symptoms of the disease. The populations of patients with PTSD and dementia are recognized, but their characteristics are largely unstudied and thus unknown.

Although the authors believe this to be a phenomenon of unrecognized coexistence of the 2 disorders, a disproportionate number of patients may be found in certain populations, especially among veterans. There is good evidence to expect increased numbers of these patients in the VA system, especially given the relative frequency of PTSD symptoms in aging cohorts of VA patients.

Click here to continue reading.

The number of veterans aged ≥ 65 years is expected to increase steadily as the Vietnam-era cohort ages. In 2012, the number of veterans aged ≥ 85 years was expected to peak at nearly 1.4 million. Vietnam-era veterans comprise the largest cohort of veterans, and > 15% of male and > 8% of female Vietnam veterans receiving care in the VA system have been diagnosed with posttraumatic stress disorder (PTSD). These veterans are rapidly approaching age groups in which cognitive disorders increase exponentially in prevalence.

Combat exposure has been called a common but “hidden variable” in studies of aging and health.¹ Combat exposure may be even more hidden for Vietnam veterans who have pursued health care outside the VA system and less likely to announce their service to health care providers.

Even veterans who did not serve in traditional combat roles can experience chronic debilitation from the psychological stress of overseas deployment to a war zone. Indeed, cases of noncombat trauma have been presented in the context of cognitive decline and late-onset PTSD.² It is probable that survivors of sexual assault, child abuse, crime, and natural disaster are also vulnerable to a recurrence of trauma symptoms if they experience cognitive slippage. In this article the authors report a case of delayed onset PTSD symptoms, precipitated by cognitive decline.

Case Report

Mr. B was a 72-year-old Korean War veteran referred for neuropsychological evaluation to establish baseline cognitive status before elective cardiac surgery. Mr. B relied on his wife to fill in many details of his personal history. His wife reported that the patient’s memory problems had increased significantly over the previous 12 months. Mr. B had been treated with donepezil 10 mg daily for about 1 year, with no observed benefit. His wife described life at home as “tense” due to his increased irritability and poor insight into his condition. Mr. B reported that he was often afraid of noises at night and needed to go outside and look around. His wife reported that he was very afraid of “strangers coming into the house.”

Mr. B was born in Arizona and experienced significant physical abuse while under the care of an alcoholic foster parent. He dropped out of high school and enlisted in the U.S. Marine Corps. Upon his discharge from military service, he worked as a truck driver for 23 years. He retired after experiencing hip problems. He drank heavily for many years after the war and, according to his wife, was “very violent,” but stopped 27 years previously, after injuring his wife while intoxicated. The patient’s medical history included hospitalization about 1 year prior to the evaluation following a fall associated with altered level of consciousness and confusion, which lasted several hours. He was discharged the same day and was thought to have had a stroke. The patient also had hypertension, hyperlipidemia, and sciatica. A carotid ultrasound showed bilateral carotid stenosis > 50%.

Mr. B was married for 45 years and had 5 children and 12 grandchildren. He enlisted in the U.S. Marine Corps at age 19 and served as a tank gunner during the Korean War. He experienced extremely heavy combat, was wounded several times (including loss of consciousness due to an explosion), and was hospitalizedfor 4 m onths in Japan. When he returned to the frontline, he found that many of the men in his unit had been killed. He was promoted to staff sergeant and tank commander. Mr. B received an honorable discharge after the war and a 50% service-connected disability pension for PTSD. He reported having received group psychotherapy at a VA hospital soon after the war but no other psychiatric treatment. He avoided watching the news because the Gulf War news reminded him of Korea.

Mr. B was smiling, pleasant, and cooperative throughout the 2 hours of testing and interviewing. He wore a Korean War veteran baseball cap festooned with military pins and ribbons, including a Purple Heart ribbon that he proudly showed to the test administrators. Unbidden, he also presented for inspection an assortment of life membership cards in various veterans service organizations. Mr. B reported frequent nightmares, night sweats, and intrusive thoughts about his combat experiences. During testing, he was repeatedly triggered by innocuous items and launched into a discourse on his combat experiences. When asked to memorize a short list of words that included the word fire, he said, “You know what that reminds me of...we had to fire big guns, 90 millimeter, that’s what it was…killing and how to kill.” When shown an abstract design that resembled the number 44, he said, “You know what that is? It was the radio call sign of our tank—‘This is 44, come in, we need some help.’”

Mr. B’s memory problems were marked by rapid forgetting, impaired ability to learn new information, and impaired ability to recall previously learned information. Language problems were also present, including difficulty recognizing and naming common objects, impaired auditory comprehension, and problems with verbal associative fluency during timed tasks. He also showed difficulties with executive functioning, attention, and working memory. His mini-mental state examination score was 21/30. He stated the year was 2020, did not know the day of the week, registered 2/3 words and recalled 0/3, he counted 3/5 in serial 7s, and was unable to repeat the phrase, “no ifs, ands, or buts.”

Discussion

Posttraumatic stress symptoms were present during the immediate aftermath of the initial trauma exposure for this patient. He managed to lead a relatively successful and productive life, sustained a marriage, and raised a family. The onset of cognitive decline precipitated a recrudescence of PTSD symptomology. In fact, the effects of combat trauma seem more malignant and extreme at the time of the memory disorders evaluation than at any prior time in his life.

A number of case reports have been published in recent years that describe comorbid presentations of cognitive disorder and PTSD symptomatology.^3-6 A clinicalconsensus that cognitive decline can exacerbate previously well-managed symptoms of earlier psychological trauma seems to be emerging. Several published casestudies have noted that comorbid presentation of dementia and PTSD is often marked by violence, psychotic symptoms, and increased risk of hospitalization.^7-9

PTSD Research

Unfortunately, systematic investigation into the relationship between PTSD and cognitive decline is in its infancy. Previous authors have posited various mechanisms to explain the exacerbation of dormant PTSD symptoms after cognitive decline.^10,11 Some have attributed the phenomenon to an age-related failure of either repression or avoidance or to a compromised ability to actively focus their attention elsewhere.^2,12 A finding of preservative errors on neuropsychological tests has been associated with an inability to organize and inhibit intrusive thought.¹³ In one case, the effects of combat trauma were purported to be denied, repressed, and largely forgotten for 30 years until rekindled by the patient’s deteriorating health and loss of employment.¹⁴ Several case examples have been presented in which physical illness, interpersonal loss, retirement, or losses of social support were other factors.^15-18 Two major studies of veterans with PTSD, found that subjects were twice as likely to develop dementia.^3,4 There is a strong association between chronic psychological stress and later development
of dementia. In a study by Wilson and colleagues, subjects with higher baseline stress had twice the chance of developing Alzheimer disease.19 Similar findings of
accelerated or higher cognitive decline were found by other studies, too.^17,20

Hippocampal damage associated with prolonged, intense psychological stress has been cited as a possible contributor to PTSD symptom recrudescence in older adults.²¹ It is well known that emotional arousal leads to better-encoded memories. In the context of a cognitive disorder marked by gradual memory loss, traumatic memories might be the last to go.²² Another proposed biologic mechanism is a reduction in hippocampal volume and decreased inhibition of the amgydala, which results in preferential recall of the nondeclarative, amygdaloidal traumatic memories.⁸

Research on selective area damage in the hippocampus opens a new era of understanding of consequences of stress. The dentate gyrus (DG) is the main area of hippocampus that helps in neurogenesis and cornus ammonis 3 (CA3) for dendritic branching.^23-25 In recent studies by Wang and colleagues, PTSD has been found to be associated with selective volume loss of the CA3/DG subfields, consistent with animal studies.^24-28 Abundance of glucocorticoid receptors in the hippocampus, especially at CA3^,29,30 may make it more vulnerable to the neurotoxic effect of glucocorticoids, causing suppression of neurogenesis,²⁹ diminished dendritic branching,30 loss of synapses,^26,31 and eventually diminished neuroplasticity,32 because CA3/DG is the main target of neurotoxicity by glucocorticoid and inflammatory damage.

The results of neuroimaging studies suggest that decreased integration of the prefrontal cortex and the hippocampus results in impaired short-term memory and perhaps increasing the prominence of long-term distressing memories.³³ Clinical observation confirms that patients with PTSD experience vivid, intense, detailed, and realistic recollections of remote memories at a time when their ability to recall nontraumatic autobiographical detail is severely compromised.

Symptom Reemergence

Both prospective and retrospective studies have shown that PTSD symptoms can evolve, even after a 20-year long symptom-free period, and reemergence of PTSD
symptoms is not uncommon.^34,35 A longer delay usually presents with less severe symptoms.³⁶ The unavailability of complete information regarding a patient’s past adjustment to psychological trauma has encouraged some experts to label exacerbation of PTSD symptoms precipitated by cognitive disorder as delayed onset PTSD. In most cases, it seems that this is more accurately described as a recrudescence of symptoms that were better managed previously. The picture is clouded by the often bizarre and extreme manifestation of PTSD symptoms in patients with memory disorders. The course of PTSD often does involve a delay between the time of exposure to trauma and symptom manifestation. In addition, symptom intensity can fluctuate significantly over the course of this often chronic illness.

The suffering associated with PTSD is often personal and concealed. Family and other collateral sources may be able to report only on social and occupational functioning. The authors recommend increased attention to proper assessment of (1) remote trauma history in patients being evaluated for memory disorders; and (2) cognitive decline in patients with history of PTSD. The problem of underreported cognitive decline is well known, although its extent is not. Early detection may help to mitigate the combined effects of these conditions. Aggressive early treatment of symptoms during the onset of cognitive dysfunction may prolong patients’ ability to remain at home.

Patient Care

Mr. B’s case was marked by significant tension in the home. Education and support of caregivers is essential to maintaining care in the least restrictive setting, such as the patient’s home. Families might be utterly bewildered by a patient’s apparently sudden preoccupation with traumatic memories. For many, this might be the first time they have ever heard the patient speak at length about the traumatic events. Simple strategies to limit exposure to distressing stimuli, improve grounding, and understand the effects of trauma can be taught. Psychopharmacologic intervention to improve sleep, slow cognitive decline, and decrease behavioral disturbances may be indicated.

Behavioral disturbance is frequently encountered when treating patients with cognitive impairment. In the limited literature on the subject, patients with both PTSD and cognitive impairment do not seem to be more prone to behavioral disturbance than patients with cognitive impairment alone.⁹ However, the case reports cited here demonstrate a high incidence of violence or potential violence in these comorbid patients. Routine assessment of potential harm from firearms or other weapons should be conducted assiduously.

It is possible that Vietnam War veterans may be more likely than previous veterans to exhibit behavioral disturbances in the context of cognitive decline and PTSD. A higher incidence of aggression, violence, and resistance to authority has been documented in this group.³⁷ Substance abuse and dependence also occurs with higher frequency in this cohort and may complicate treatment of cognitive impairment and PTSD.^38,39 A large number of these veterans may initially present to non-VA health care providers and these clinicians may be unaware of a patient’s prior combat exposure and thus fail to accurately assess PTSD.

Although the relation of PTSD and vulnerability to dementia has been well established, it is unknown how the presence of PTSD symptomatology impacts dementia symptoms or how the presence of dementia impacts PTSD symptoms. Posttraumatic stress disorder and dementia share similar risks like traumatic brain injury, low IQ, poor education, substance abuse, precipitated by stressful life events and impairment of coping, physical health and related risk factors. Unmasking PTSD symptoms resulting from dementia is a well-known phenomenon described in recent studies on late-onset stress symptomatology (LOSS).^5,10,40

Since PTSD is a major risk factor that doubles the chance of developing dementia, mandatory screening for dementia in older patients along with assessment of other risk factors as a standard of care may help physicians in the early detection and initiation of care. Recognition of LOSS may be an important milestone in the treatment of delayed onset PTSD, which is considered a normal aging process and a premorbid stage of PTSD.^10,40

Although there is no established treatment, early psychotherapeutic approaches like reminiscent therapy along with psychoeducation may be beneficial in patients with LOSS.^40-42 Effective treatments for PTSD with patients with dementia may be challenging, though dementia was not found to be a barrier to implement prolonged exposure therapy in patients with mild cognitive impairment.43 Patient aligned care teams can be an ideal approach for the care of these veterans.

Conclusion

Posttraumatic stress disorder and dementia are well studied and documented disorders, although PTSD has been studied far more extensively in younger populations. Accounts of comorbidity of the 2 disorders are limited in the literature. Individuals may exhibit PTSD symptoms prior to the onset of dementia. They also may develop or uncover long quiescent symptoms of the disease. The populations of patients with PTSD and dementia are recognized, but their characteristics are largely unstudied and thus unknown.

Although the authors believe this to be a phenomenon of unrecognized coexistence of the 2 disorders, a disproportionate number of patients may be found in certain populations, especially among veterans. There is good evidence to expect increased numbers of these patients in the VA system, especially given the relative frequency of PTSD symptoms in aging cohorts of VA patients.

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Case

A 34-year-old woman presented to the ED with severe, persistent abdominal pain that had begun 18 days earlier. She was 7 weeks pregnant and had been seen in the same ED the day before. During that visit, ultrasound had shown a single pregnancy of doubtful viability. Abdominal magnetic resonance imaging was normal. She was given multiple doses of hydromorphone. The discharge diagnosis was “missed abortion.”

Since the onset of her pain, she had been hospitalized twice elsewhere, with no clear diagnosis to explain her pain. Treatment consisted of repeat doses of hydromorphone. During the second hospitalization, a sodium level of 109 mEq/L had been corrected with hypertonic saline, and a urinary tract infection (UTI) had been treated with cephalexin.

Our patient had never experienced similar abdominal pain. Her medical history included depression and asthma. Her family history was notable for an aunt who had died of lung cancer.

On this ED visit, the patient’s vital signs were normal. On examination, she was moaning in pain and clutching her abdomen. The abdomen was tender in both lower quadrants, with guarding but no rebound. Her sodium level was 125 mEq/L; the day before it had been 132 mEq/L.

Urine dipstick testing showed 2+ glucose and 2+ bilirubin; both had been within normal range (negative) the day before. An abdominal/pelvic computed tomography scan with intravenous (IV) and oral contrast did not reveal any potential cause of the patient’s pain. Multiple doses of IV hydromorphone were given, but her pain persisted.

We revisited our patient’s family history. With prompting, she remembered that as a teenager, her mother had had an illness that caused “problems with her nerves and blood vessels and turned her urine red.” When reached by phone, the patient’s mother, who lives outside the United States, said she was familiar with the term “porphyria,” but curiously, she did not state she carried the diagnosis, and had not advised her children they could be at risk.

The patient was admitted to the intensive care unit (ICU) for treatment of hyponatremia. Her mother’s history led us to suspect porphyria, so we sent a urine sample from the ED for porphobilinogen (PBG) testing. Her urine was not red at that time (on further questioning, she remembered she had had an episode of “red urine” recently). Two days later, after the PBG result came back positive, treatment was initiated for porphyria. With further stool and serum testing, the diagnosis of acute intermittent porphyria (AIP) was made.

The patient was treated with glucose loading and hemin therapy. In the ICU, 2 ampules of 50% dextrose in water solution (D50W) was administered, and she was transferred to the hematology-oncology service for hemin therapy. Soon after, she underwent a dilation and curettage. Three weeks later, she was discharged in good condition.

Discussion

The unifying diagnostic concept is that toxins damage all components of the nervous system: intestinal, central, peripheral, and autonomic. Hence, any combination of abdominal pain, vomiting, psychiatric symptoms, vital sign instability, weakness, or sensory loss may occur.¹ To further confuse the diagnostician, the constellation of symptoms may vary with each episode.

Two critical laboratory clues are red urine—which often is mistaken for a UTI or hematuria—and hyponatremia.¹ Another porphyria hallmark is triggers. These include drugs, carbohydrate deprivation, smoking, and stress. Common chemical inciters include alcohol, ketamine, etomidate, macrodantin, nifedipine, progesterone, and phenytoin.¹ The Atkins diet (zero carbohydrates) reportedly caused an uptick in new porphyria cases.¹

Attacks usually start after puberty. Women tend to experience flares during the luteal (progesterone) phase of the menstrual cycle.¹ Acute intermittent porphyria can mimic Guillain-Barré syndrome and psychosis.² Delayed diagnosis may lead to irreversible neurological damage or death.²

Despite AIP’s complexity, initial diagnostic testing is simple: a urinary PBG level obtained during an attack is virtually 100% sensitive and specific for AIP and two other acute porphyrias: hereditary coproporphyria (HCP), and variegate porphyria (VP). A positive urine PBG mandates immediate treatment—even while awaiting porphyrin and GK delta-aminolevulinic acid (ALA) levels in stool and serum to identify which porphyria (AIP, HCP, or VP) is present. The fourth (and least common) acute porphyria, ALA dehydratase porphyria (ADP), may produce no PBG elevation and requires separate porphyrin and ALA testing to make the diagnosis.

Treatment

Treatment targets runaway heme precursor synthesis at its start and finish (Figure). Glucose-loading suppresses the initial enzyme, ALA synthase. Since the absence of normal end-product (heme) drives the enzymatic cascade, addition of IV hemin provides the substrate—and negative feedback—to stop it.

Conclusion

This case represents an example of AIP in which a patient presented with the characteristic abdominal pain and hyponatremia, complicated by the fact that she was pregnant and her urine was not red.

Intractable abdominal pain with negative imaging must prompt a search for red urine, neurological symptoms, porphyria medication triggers, and a family history of porphyria. Any constellation of findings should prompt immediate urine PBG testing.

In the appropriate clinical setting, it may be prudent to glucose-load a patient while waiting for confirmatory testing (which can take 1-2 days). Hemin therapy is best instituted by the hematology service after high urine PBG levels are confirmed.

Case

A 34-year-old woman presented to the ED with severe, persistent abdominal pain that had begun 18 days earlier. She was 7 weeks pregnant and had been seen in the same ED the day before. During that visit, ultrasound had shown a single pregnancy of doubtful viability. Abdominal magnetic resonance imaging was normal. She was given multiple doses of hydromorphone. The discharge diagnosis was “missed abortion.”

Since the onset of her pain, she had been hospitalized twice elsewhere, with no clear diagnosis to explain her pain. Treatment consisted of repeat doses of hydromorphone. During the second hospitalization, a sodium level of 109 mEq/L had been corrected with hypertonic saline, and a urinary tract infection (UTI) had been treated with cephalexin.

Our patient had never experienced similar abdominal pain. Her medical history included depression and asthma. Her family history was notable for an aunt who had died of lung cancer.

On this ED visit, the patient’s vital signs were normal. On examination, she was moaning in pain and clutching her abdomen. The abdomen was tender in both lower quadrants, with guarding but no rebound. Her sodium level was 125 mEq/L; the day before it had been 132 mEq/L.

Urine dipstick testing showed 2+ glucose and 2+ bilirubin; both had been within normal range (negative) the day before. An abdominal/pelvic computed tomography scan with intravenous (IV) and oral contrast did not reveal any potential cause of the patient’s pain. Multiple doses of IV hydromorphone were given, but her pain persisted.

We revisited our patient’s family history. With prompting, she remembered that as a teenager, her mother had had an illness that caused “problems with her nerves and blood vessels and turned her urine red.” When reached by phone, the patient’s mother, who lives outside the United States, said she was familiar with the term “porphyria,” but curiously, she did not state she carried the diagnosis, and had not advised her children they could be at risk.

The patient was admitted to the intensive care unit (ICU) for treatment of hyponatremia. Her mother’s history led us to suspect porphyria, so we sent a urine sample from the ED for porphobilinogen (PBG) testing. Her urine was not red at that time (on further questioning, she remembered she had had an episode of “red urine” recently). Two days later, after the PBG result came back positive, treatment was initiated for porphyria. With further stool and serum testing, the diagnosis of acute intermittent porphyria (AIP) was made.

The patient was treated with glucose loading and hemin therapy. In the ICU, 2 ampules of 50% dextrose in water solution (D50W) was administered, and she was transferred to the hematology-oncology service for hemin therapy. Soon after, she underwent a dilation and curettage. Three weeks later, she was discharged in good condition.

Discussion

The unifying diagnostic concept is that toxins damage all components of the nervous system: intestinal, central, peripheral, and autonomic. Hence, any combination of abdominal pain, vomiting, psychiatric symptoms, vital sign instability, weakness, or sensory loss may occur.¹ To further confuse the diagnostician, the constellation of symptoms may vary with each episode.

Two critical laboratory clues are red urine—which often is mistaken for a UTI or hematuria—and hyponatremia.¹ Another porphyria hallmark is triggers. These include drugs, carbohydrate deprivation, smoking, and stress. Common chemical inciters include alcohol, ketamine, etomidate, macrodantin, nifedipine, progesterone, and phenytoin.¹ The Atkins diet (zero carbohydrates) reportedly caused an uptick in new porphyria cases.¹

Attacks usually start after puberty. Women tend to experience flares during the luteal (progesterone) phase of the menstrual cycle.¹ Acute intermittent porphyria can mimic Guillain-Barré syndrome and psychosis.² Delayed diagnosis may lead to irreversible neurological damage or death.²

Despite AIP’s complexity, initial diagnostic testing is simple: a urinary PBG level obtained during an attack is virtually 100% sensitive and specific for AIP and two other acute porphyrias: hereditary coproporphyria (HCP), and variegate porphyria (VP). A positive urine PBG mandates immediate treatment—even while awaiting porphyrin and GK delta-aminolevulinic acid (ALA) levels in stool and serum to identify which porphyria (AIP, HCP, or VP) is present. The fourth (and least common) acute porphyria, ALA dehydratase porphyria (ADP), may produce no PBG elevation and requires separate porphyrin and ALA testing to make the diagnosis.

Treatment

Treatment targets runaway heme precursor synthesis at its start and finish (Figure). Glucose-loading suppresses the initial enzyme, ALA synthase. Since the absence of normal end-product (heme) drives the enzymatic cascade, addition of IV hemin provides the substrate—and negative feedback—to stop it.

Conclusion

This case represents an example of AIP in which a patient presented with the characteristic abdominal pain and hyponatremia, complicated by the fact that she was pregnant and her urine was not red.

Intractable abdominal pain with negative imaging must prompt a search for red urine, neurological symptoms, porphyria medication triggers, and a family history of porphyria. Any constellation of findings should prompt immediate urine PBG testing.

In the appropriate clinical setting, it may be prudent to glucose-load a patient while waiting for confirmatory testing (which can take 1-2 days). Hemin therapy is best instituted by the hematology service after high urine PBG levels are confirmed.

Case

A 34-year-old woman presented to the ED with severe, persistent abdominal pain that had begun 18 days earlier. She was 7 weeks pregnant and had been seen in the same ED the day before. During that visit, ultrasound had shown a single pregnancy of doubtful viability. Abdominal magnetic resonance imaging was normal. She was given multiple doses of hydromorphone. The discharge diagnosis was “missed abortion.”

Since the onset of her pain, she had been hospitalized twice elsewhere, with no clear diagnosis to explain her pain. Treatment consisted of repeat doses of hydromorphone. During the second hospitalization, a sodium level of 109 mEq/L had been corrected with hypertonic saline, and a urinary tract infection (UTI) had been treated with cephalexin.

Our patient had never experienced similar abdominal pain. Her medical history included depression and asthma. Her family history was notable for an aunt who had died of lung cancer.

On this ED visit, the patient’s vital signs were normal. On examination, she was moaning in pain and clutching her abdomen. The abdomen was tender in both lower quadrants, with guarding but no rebound. Her sodium level was 125 mEq/L; the day before it had been 132 mEq/L.

Urine dipstick testing showed 2+ glucose and 2+ bilirubin; both had been within normal range (negative) the day before. An abdominal/pelvic computed tomography scan with intravenous (IV) and oral contrast did not reveal any potential cause of the patient’s pain. Multiple doses of IV hydromorphone were given, but her pain persisted.

We revisited our patient’s family history. With prompting, she remembered that as a teenager, her mother had had an illness that caused “problems with her nerves and blood vessels and turned her urine red.” When reached by phone, the patient’s mother, who lives outside the United States, said she was familiar with the term “porphyria,” but curiously, she did not state she carried the diagnosis, and had not advised her children they could be at risk.

The patient was admitted to the intensive care unit (ICU) for treatment of hyponatremia. Her mother’s history led us to suspect porphyria, so we sent a urine sample from the ED for porphobilinogen (PBG) testing. Her urine was not red at that time (on further questioning, she remembered she had had an episode of “red urine” recently). Two days later, after the PBG result came back positive, treatment was initiated for porphyria. With further stool and serum testing, the diagnosis of acute intermittent porphyria (AIP) was made.

The patient was treated with glucose loading and hemin therapy. In the ICU, 2 ampules of 50% dextrose in water solution (D50W) was administered, and she was transferred to the hematology-oncology service for hemin therapy. Soon after, she underwent a dilation and curettage. Three weeks later, she was discharged in good condition.

Discussion

The unifying diagnostic concept is that toxins damage all components of the nervous system: intestinal, central, peripheral, and autonomic. Hence, any combination of abdominal pain, vomiting, psychiatric symptoms, vital sign instability, weakness, or sensory loss may occur.¹ To further confuse the diagnostician, the constellation of symptoms may vary with each episode.

Two critical laboratory clues are red urine—which often is mistaken for a UTI or hematuria—and hyponatremia.¹ Another porphyria hallmark is triggers. These include drugs, carbohydrate deprivation, smoking, and stress. Common chemical inciters include alcohol, ketamine, etomidate, macrodantin, nifedipine, progesterone, and phenytoin.¹ The Atkins diet (zero carbohydrates) reportedly caused an uptick in new porphyria cases.¹

Attacks usually start after puberty. Women tend to experience flares during the luteal (progesterone) phase of the menstrual cycle.¹ Acute intermittent porphyria can mimic Guillain-Barré syndrome and psychosis.² Delayed diagnosis may lead to irreversible neurological damage or death.²

Despite AIP’s complexity, initial diagnostic testing is simple: a urinary PBG level obtained during an attack is virtually 100% sensitive and specific for AIP and two other acute porphyrias: hereditary coproporphyria (HCP), and variegate porphyria (VP). A positive urine PBG mandates immediate treatment—even while awaiting porphyrin and GK delta-aminolevulinic acid (ALA) levels in stool and serum to identify which porphyria (AIP, HCP, or VP) is present. The fourth (and least common) acute porphyria, ALA dehydratase porphyria (ADP), may produce no PBG elevation and requires separate porphyrin and ALA testing to make the diagnosis.

Treatment

Treatment targets runaway heme precursor synthesis at its start and finish (Figure). Glucose-loading suppresses the initial enzyme, ALA synthase. Since the absence of normal end-product (heme) drives the enzymatic cascade, addition of IV hemin provides the substrate—and negative feedback—to stop it.

Conclusion

This case represents an example of AIP in which a patient presented with the characteristic abdominal pain and hyponatremia, complicated by the fact that she was pregnant and her urine was not red.

Intractable abdominal pain with negative imaging must prompt a search for red urine, neurological symptoms, porphyria medication triggers, and a family history of porphyria. Any constellation of findings should prompt immediate urine PBG testing.

In the appropriate clinical setting, it may be prudent to glucose-load a patient while waiting for confirmatory testing (which can take 1-2 days). Hemin therapy is best instituted by the hematology service after high urine PBG levels are confirmed.

Intra-articular corticosteroid injections (CSIs) have been a common treatment for osteoarthritis since the 1950s and continue to be an option for patients who prefer nonoperative management.¹ Although CSIs may improve pain secondary to osteoarthritis temporarily, they do not slow articular cartilage degradation, and many patients request multiple CSIs before total joint arthroplasty ultimately is required.^1,2 Therefore, acute and chronic side effects of CSI must be considered when repeatedly administering corticosteroids.

A postinjection flare, the most common acute side effect of intra-articular CSI, is characterized by a localized inflammatory response that can last 2 to 3 days. The flare occurs in 2% to 25% of CSI cases.^3-5 Symptoms can range from mild joint effusion to disabling pain.⁶ In the present case, a severe postinjection flare occurred after intra-articular administration of triamcinolone acetonide (Kenalog). This case is novel in that its acuity of onset, severity of symptoms, and synovial fluid analysis mimicked septic arthritis, which was ultimately ruled out with negative cultures and confirmation of triamcinolone acetonide crystals in the synovial aspirate, viewed by polarized light microscopy. To date, only one other case of an immediate (<2 hours) and severe postinjection flare in response to triamcinolone has been reported.⁷ As CSIs are often used in the nonoperative treatment of osteoarthritis, it is imperative for the treating physician to be aware of this potential side effect in order to appropriately inform the patient of this risk and guide treatment should the scenario arise. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 56-year-old woman with a history of hypertension, hypothyroidism, and moderate bilateral knee osteoarthritis presented with left knee pain. She had been receiving annual hylan injections for 5 years and had no adverse reactions, but the pain gradually worsened over the past 3 months. She was given an intra-articular injection of 2 mL of 1% lidocaine and 2 mL (40 mg) of triamcinolone acetonide in the left knee.

Two hours later, she experienced swelling and intense pain in the knee and was unable to ambulate. Physical examination revealed she was afebrile but was having severe pain in the knee through all range of motion. The knee had no appreciable erythema or warmth. Laboratory data were significant: White blood cell (WBC) count was 14,600, and erythrocyte sedimentation rate was 1 mm/h. The knee was aspirated with a return of 25 mL of “butterscotch”-colored fluid (Figure 1). The patient was admitted to rule out iatrogenic septic arthritis, or chronic, indolent septic arthritis acutely worsened by CSI, until synovial fluid analysis and cultures could be performed (Table 1).

She was treated overnight with a compressive wrap, elevation, ice, and nonsteroidal anti-inflammatory drugs, which provided significant pain relief. Polarized light microscopy revealed polymorphic intracellular and extracellular crystals with crystal morphology consistent with the injection of triamcinolone ester (Figure 2). Gram stain showed many WBCs but no organisms. These findings were thought to represent an exogenous crystal-induced acute inflammatory response. Given the patient’s improving clinical course, she was discharged the next morning.

Twelve days later, at clinic follow-up, she was still experiencing pain above her baseline level. Given the continued effusion, 8 mL of synovial fluid was aspirated, which appeared clear and only slightly blood-tinged. Synovial analysis showed resolution of leukocytosis, confirming a severe postinjection flare in response to triamcinolone acetonide.

Discussion

Although rare, side effects from repeated intra-articular CSIs include hypothalamic-pituitary-adrenal axis dysfunction and steroid-induced myopathy.^8,9 Acute side effects are more common and include postinjection flare, iatrogenic septic arthritis, local tissue atrophy, cartilage damage, tendon rupture, nerve atrophy, increased blood glucose, and osteonecrosis.^10,11 The present case report describes an extreme example of a postinjection flare in response to triamcinolone acetonide and summarizes the characteristics of injections that cause flares.

The physical properties of corticosteroids have a significant impact on their efficacy and on their potential for adverse events. Corticosteroid preparations can be water-soluble or water-insoluble. Most commonly, water-insoluble preparations that contain insoluble corticosteroid esters (eg, triamcinolone, methylprednisolone) are used in intra-articular injections. These form microcrystalline aggregates in solution, which require the patient’s own hydrolytic enzymes (esterases) to release the active moiety and thus have a longer duration of action. However, they are more commonly associated with postinjection flares compared with their more soluble and faster- acting counterparts (eg. dexamethasone, betamethasone).¹⁰ Microcrystalline aggregates, which are larger in size, induce a stronger inflammatory response, and in a dose-dependent manner.6A sterile inflammatory reaction to hydrocortisone, cortisone, dexamethasone, triamcinolone, and prednisolone crystals in normal joints has been previously described,6,12,13 and crystals of the various preparations have been demonstrated within leukocytes by both polarized light and electron microscopy.^12,13 Table 2 summarizes previous synovial fluid analyses after intra-articular injections of various corticosteroid preparations in normal healthy joints and in patients experiencing a postinjection flare. To date, there have been no reports of an immediate (<2 hours) and severe postinjection flare in response to triamcinolone acetonide, though there was a report of a postinjection flare in response to triamcinolone hexacetonide (Aristospan),⁷ and here the synovial fluid WBC count (30,000) was much lower.

Although many cases of corticosteroid hypersensitivity have been reported, in rare cases intra-articular administration of triamcinolone has caused anaphylactic reactions and shock.^14,15 Multiple case studies have determined that the specific excipient carboxymethylcellulose (found in many triamcinolone preparations), and not the corticosteroid itself, can cause an immunoglobulin E–mediated anaphylactic reaction.^16-18 Therefore, performing skin-prick tests for potential corticosteroids and their excipients in patients with known postinjection flares might help prevent serious adverse reactions.^18,19

The present case involved an extreme postinjection flare in response to intra-articular administration of triamcinolone acetonide. Postinjection flares are rare but significant events, and physicians using CSIs in the treatment of arthritis need to be aware of this potential reaction in order to appropriately inform patients of this risk and guide treatment should the scenario arise.

Intra-articular corticosteroid injections (CSIs) have been a common treatment for osteoarthritis since the 1950s and continue to be an option for patients who prefer nonoperative management.¹ Although CSIs may improve pain secondary to osteoarthritis temporarily, they do not slow articular cartilage degradation, and many patients request multiple CSIs before total joint arthroplasty ultimately is required.^1,2 Therefore, acute and chronic side effects of CSI must be considered when repeatedly administering corticosteroids.

A postinjection flare, the most common acute side effect of intra-articular CSI, is characterized by a localized inflammatory response that can last 2 to 3 days. The flare occurs in 2% to 25% of CSI cases.^3-5 Symptoms can range from mild joint effusion to disabling pain.⁶ In the present case, a severe postinjection flare occurred after intra-articular administration of triamcinolone acetonide (Kenalog). This case is novel in that its acuity of onset, severity of symptoms, and synovial fluid analysis mimicked septic arthritis, which was ultimately ruled out with negative cultures and confirmation of triamcinolone acetonide crystals in the synovial aspirate, viewed by polarized light microscopy. To date, only one other case of an immediate (<2 hours) and severe postinjection flare in response to triamcinolone has been reported.⁷ As CSIs are often used in the nonoperative treatment of osteoarthritis, it is imperative for the treating physician to be aware of this potential side effect in order to appropriately inform the patient of this risk and guide treatment should the scenario arise. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 56-year-old woman with a history of hypertension, hypothyroidism, and moderate bilateral knee osteoarthritis presented with left knee pain. She had been receiving annual hylan injections for 5 years and had no adverse reactions, but the pain gradually worsened over the past 3 months. She was given an intra-articular injection of 2 mL of 1% lidocaine and 2 mL (40 mg) of triamcinolone acetonide in the left knee.

Two hours later, she experienced swelling and intense pain in the knee and was unable to ambulate. Physical examination revealed she was afebrile but was having severe pain in the knee through all range of motion. The knee had no appreciable erythema or warmth. Laboratory data were significant: White blood cell (WBC) count was 14,600, and erythrocyte sedimentation rate was 1 mm/h. The knee was aspirated with a return of 25 mL of “butterscotch”-colored fluid (Figure 1). The patient was admitted to rule out iatrogenic septic arthritis, or chronic, indolent septic arthritis acutely worsened by CSI, until synovial fluid analysis and cultures could be performed (Table 1).

She was treated overnight with a compressive wrap, elevation, ice, and nonsteroidal anti-inflammatory drugs, which provided significant pain relief. Polarized light microscopy revealed polymorphic intracellular and extracellular crystals with crystal morphology consistent with the injection of triamcinolone ester (Figure 2). Gram stain showed many WBCs but no organisms. These findings were thought to represent an exogenous crystal-induced acute inflammatory response. Given the patient’s improving clinical course, she was discharged the next morning.

Twelve days later, at clinic follow-up, she was still experiencing pain above her baseline level. Given the continued effusion, 8 mL of synovial fluid was aspirated, which appeared clear and only slightly blood-tinged. Synovial analysis showed resolution of leukocytosis, confirming a severe postinjection flare in response to triamcinolone acetonide.

Discussion

Although rare, side effects from repeated intra-articular CSIs include hypothalamic-pituitary-adrenal axis dysfunction and steroid-induced myopathy.^8,9 Acute side effects are more common and include postinjection flare, iatrogenic septic arthritis, local tissue atrophy, cartilage damage, tendon rupture, nerve atrophy, increased blood glucose, and osteonecrosis.^10,11 The present case report describes an extreme example of a postinjection flare in response to triamcinolone acetonide and summarizes the characteristics of injections that cause flares.

The physical properties of corticosteroids have a significant impact on their efficacy and on their potential for adverse events. Corticosteroid preparations can be water-soluble or water-insoluble. Most commonly, water-insoluble preparations that contain insoluble corticosteroid esters (eg, triamcinolone, methylprednisolone) are used in intra-articular injections. These form microcrystalline aggregates in solution, which require the patient’s own hydrolytic enzymes (esterases) to release the active moiety and thus have a longer duration of action. However, they are more commonly associated with postinjection flares compared with their more soluble and faster- acting counterparts (eg. dexamethasone, betamethasone).¹⁰ Microcrystalline aggregates, which are larger in size, induce a stronger inflammatory response, and in a dose-dependent manner.6A sterile inflammatory reaction to hydrocortisone, cortisone, dexamethasone, triamcinolone, and prednisolone crystals in normal joints has been previously described,6,12,13 and crystals of the various preparations have been demonstrated within leukocytes by both polarized light and electron microscopy.^12,13 Table 2 summarizes previous synovial fluid analyses after intra-articular injections of various corticosteroid preparations in normal healthy joints and in patients experiencing a postinjection flare. To date, there have been no reports of an immediate (<2 hours) and severe postinjection flare in response to triamcinolone acetonide, though there was a report of a postinjection flare in response to triamcinolone hexacetonide (Aristospan),⁷ and here the synovial fluid WBC count (30,000) was much lower.

Although many cases of corticosteroid hypersensitivity have been reported, in rare cases intra-articular administration of triamcinolone has caused anaphylactic reactions and shock.^14,15 Multiple case studies have determined that the specific excipient carboxymethylcellulose (found in many triamcinolone preparations), and not the corticosteroid itself, can cause an immunoglobulin E–mediated anaphylactic reaction.^16-18 Therefore, performing skin-prick tests for potential corticosteroids and their excipients in patients with known postinjection flares might help prevent serious adverse reactions.^18,19

The present case involved an extreme postinjection flare in response to intra-articular administration of triamcinolone acetonide. Postinjection flares are rare but significant events, and physicians using CSIs in the treatment of arthritis need to be aware of this potential reaction in order to appropriately inform patients of this risk and guide treatment should the scenario arise.

Intra-articular corticosteroid injections (CSIs) have been a common treatment for osteoarthritis since the 1950s and continue to be an option for patients who prefer nonoperative management.¹ Although CSIs may improve pain secondary to osteoarthritis temporarily, they do not slow articular cartilage degradation, and many patients request multiple CSIs before total joint arthroplasty ultimately is required.^1,2 Therefore, acute and chronic side effects of CSI must be considered when repeatedly administering corticosteroids.

A postinjection flare, the most common acute side effect of intra-articular CSI, is characterized by a localized inflammatory response that can last 2 to 3 days. The flare occurs in 2% to 25% of CSI cases.^3-5 Symptoms can range from mild joint effusion to disabling pain.⁶ In the present case, a severe postinjection flare occurred after intra-articular administration of triamcinolone acetonide (Kenalog). This case is novel in that its acuity of onset, severity of symptoms, and synovial fluid analysis mimicked septic arthritis, which was ultimately ruled out with negative cultures and confirmation of triamcinolone acetonide crystals in the synovial aspirate, viewed by polarized light microscopy. To date, only one other case of an immediate (<2 hours) and severe postinjection flare in response to triamcinolone has been reported.⁷ As CSIs are often used in the nonoperative treatment of osteoarthritis, it is imperative for the treating physician to be aware of this potential side effect in order to appropriately inform the patient of this risk and guide treatment should the scenario arise. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 56-year-old woman with a history of hypertension, hypothyroidism, and moderate bilateral knee osteoarthritis presented with left knee pain. She had been receiving annual hylan injections for 5 years and had no adverse reactions, but the pain gradually worsened over the past 3 months. She was given an intra-articular injection of 2 mL of 1% lidocaine and 2 mL (40 mg) of triamcinolone acetonide in the left knee.

Two hours later, she experienced swelling and intense pain in the knee and was unable to ambulate. Physical examination revealed she was afebrile but was having severe pain in the knee through all range of motion. The knee had no appreciable erythema or warmth. Laboratory data were significant: White blood cell (WBC) count was 14,600, and erythrocyte sedimentation rate was 1 mm/h. The knee was aspirated with a return of 25 mL of “butterscotch”-colored fluid (Figure 1). The patient was admitted to rule out iatrogenic septic arthritis, or chronic, indolent septic arthritis acutely worsened by CSI, until synovial fluid analysis and cultures could be performed (Table 1).

She was treated overnight with a compressive wrap, elevation, ice, and nonsteroidal anti-inflammatory drugs, which provided significant pain relief. Polarized light microscopy revealed polymorphic intracellular and extracellular crystals with crystal morphology consistent with the injection of triamcinolone ester (Figure 2). Gram stain showed many WBCs but no organisms. These findings were thought to represent an exogenous crystal-induced acute inflammatory response. Given the patient’s improving clinical course, she was discharged the next morning.

Twelve days later, at clinic follow-up, she was still experiencing pain above her baseline level. Given the continued effusion, 8 mL of synovial fluid was aspirated, which appeared clear and only slightly blood-tinged. Synovial analysis showed resolution of leukocytosis, confirming a severe postinjection flare in response to triamcinolone acetonide.

Discussion

Although rare, side effects from repeated intra-articular CSIs include hypothalamic-pituitary-adrenal axis dysfunction and steroid-induced myopathy.^8,9 Acute side effects are more common and include postinjection flare, iatrogenic septic arthritis, local tissue atrophy, cartilage damage, tendon rupture, nerve atrophy, increased blood glucose, and osteonecrosis.^10,11 The present case report describes an extreme example of a postinjection flare in response to triamcinolone acetonide and summarizes the characteristics of injections that cause flares.

The physical properties of corticosteroids have a significant impact on their efficacy and on their potential for adverse events. Corticosteroid preparations can be water-soluble or water-insoluble. Most commonly, water-insoluble preparations that contain insoluble corticosteroid esters (eg, triamcinolone, methylprednisolone) are used in intra-articular injections. These form microcrystalline aggregates in solution, which require the patient’s own hydrolytic enzymes (esterases) to release the active moiety and thus have a longer duration of action. However, they are more commonly associated with postinjection flares compared with their more soluble and faster- acting counterparts (eg. dexamethasone, betamethasone).¹⁰ Microcrystalline aggregates, which are larger in size, induce a stronger inflammatory response, and in a dose-dependent manner.6A sterile inflammatory reaction to hydrocortisone, cortisone, dexamethasone, triamcinolone, and prednisolone crystals in normal joints has been previously described,6,12,13 and crystals of the various preparations have been demonstrated within leukocytes by both polarized light and electron microscopy.^12,13 Table 2 summarizes previous synovial fluid analyses after intra-articular injections of various corticosteroid preparations in normal healthy joints and in patients experiencing a postinjection flare. To date, there have been no reports of an immediate (<2 hours) and severe postinjection flare in response to triamcinolone acetonide, though there was a report of a postinjection flare in response to triamcinolone hexacetonide (Aristospan),⁷ and here the synovial fluid WBC count (30,000) was much lower.

Although many cases of corticosteroid hypersensitivity have been reported, in rare cases intra-articular administration of triamcinolone has caused anaphylactic reactions and shock.^14,15 Multiple case studies have determined that the specific excipient carboxymethylcellulose (found in many triamcinolone preparations), and not the corticosteroid itself, can cause an immunoglobulin E–mediated anaphylactic reaction.^16-18 Therefore, performing skin-prick tests for potential corticosteroids and their excipients in patients with known postinjection flares might help prevent serious adverse reactions.^18,19

The present case involved an extreme postinjection flare in response to intra-articular administration of triamcinolone acetonide. Postinjection flares are rare but significant events, and physicians using CSIs in the treatment of arthritis need to be aware of this potential reaction in order to appropriately inform patients of this risk and guide treatment should the scenario arise.

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm.

Click on the PDF icon at the top of this introduction to read the full article.​

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm.

Click on the PDF icon at the top of this introduction to read the full article.​

T-cell prolymphocytic leukemia (T-PLL) is a rare malignancy that comprises about 2% of all mature lymphoid neoplasms. Patients usually present with prominent peripheral blood lymphocytosis, splenomegaly, hepatomegaly, lymphadenopathy, B symptoms, and occasionally with skin lesions.¹ The disease follows an aggressive clinical course with rapid progression and typically has a median survival of less than 1 year. In some cases, the disease is indolent for a period of time before becoming aggressive.² In 2002, 7 years after initial diagnosis in 1995, the case discussed herein was reported as a rare, indolent form of T-PLL.³ We now present 11 additional years of follow-up of this case, during which time the patient remained asymptomatic with respect to his lymphoid neoplasm.

Click on the PDF icon at the top of this introduction to read the full article.​

Primary bladder adenocarcinoma  is an epithelial malignancy with pure glandular differentiation, without evidence of typical urothelial (transitional cell) carcinoma. PBA is rare, accounting for 0.5%-2% of all malignant bladder neoplasms, and it is seen more frequently in men than in women and is commonly diagnosed in the sixth decade of life.^1-3 Clinical presentation includes hematuria and symptoms of bladder irritation.²

Click on the PDF icon at the top of this introduction to read the full article.

Primary bladder adenocarcinoma  is an epithelial malignancy with pure glandular differentiation, without evidence of typical urothelial (transitional cell) carcinoma. PBA is rare, accounting for 0.5%-2% of all malignant bladder neoplasms, and it is seen more frequently in men than in women and is commonly diagnosed in the sixth decade of life.^1-3 Clinical presentation includes hematuria and symptoms of bladder irritation.²

Click on the PDF icon at the top of this introduction to read the full article.

Primary bladder adenocarcinoma  is an epithelial malignancy with pure glandular differentiation, without evidence of typical urothelial (transitional cell) carcinoma. PBA is rare, accounting for 0.5%-2% of all malignant bladder neoplasms, and it is seen more frequently in men than in women and is commonly diagnosed in the sixth decade of life.^1-3 Clinical presentation includes hematuria and symptoms of bladder irritation.²

Click on the PDF icon at the top of this introduction to read the full article.

Total hip arthroplasty (THA) is considered to be one of the most successful orthopedic interventions of its generation.¹ In 2010, 332,000 THAs were performed in the U.S.² Although used to correct advanced joint diseases in the elderly, the THA procedure has become increasingly common in a younger population for posttraumatic fractures and conditions that lead to early onset secondary arthritis such as avascular necrosis, juvenile rheumatoid arthritis, hip dysplasia, Perthes disease, and femoro-acetabular impingement.

Current hip replacements are expected to function at least 10 to 20 years in 90% of patients.³ As increasing numbers of young patients have these procedures and as seniors continue to live longer, patients will outlast their implants. Younger and more active patients have a higher rate of revision, because the longevity of the prosthesis is usually a function of usage.³ The number of revision THAs is projected to increase 137% by 2030.⁴

Hip resurfacing has been developed as a bone preserving surgical alternative to THA. The first system for use in the U.S. received FDA approval in 2006, but concerns about the metal on metal bearing surfaces, high failure and revision rates, and early catastrophic modes of failure compared with THAs has resulted in the recall of many of these devices. Hip resurfacing may offer some advantages compared with those of a THA in a carefully selected population, but its use will not be further discussed in this case study.⁵ Periprosthetic osteolysis and aseptic loosening are 2 of the long-term consequences of THA.⁶ Bone loss is felt to be secondary to a biologic reaction to particulate debris from implants.⁶ Some patients, especially those with loosening, complete wear, or fracture, will be symptomatic with pain. However, wear and osteolysis is a silent disease unless there is mechanical failure. Other patients may not experience discomfort. Radiographic studies may reveal significant changes, which warrant the recommendation for a hip revision.

Hip revision surgery has 3 major purposes: relieving pain in the affected joint, restoring the patient’s mobility, and removing a loose or damaged prosthesis before irreversible harm is done to the joint. It’s anticipated that most primary care providers (PCPs) will encounter patients who seek advice on the need for a revision hip arthroplasty.

This case will present an asymptomatic patient who underwent a THA in 1997 at age 37, to address developmental dysplasia of the hip (DDH) and was advised to undergo a revision hip arthroplasty due to abnormal radiographic findings at age 55 years. A discussion will follow that includes a brief review of the history of THA, the materials and bearings commonly used, the presenting symptoms or radiographic changes that signal the need for a revision, and the current options available for a patient such as this.

Case Report

A man aged 55 years presented to a new orthopedic surgeon for his first orthopedic appointment in 10 years. The patient had a left metal-on-polyethylene (M-on-PE) THA 18 years prior due to early onset secondary degenerative joint disease from DDH. The patient’s M-on-PE THA was a titanium acetabular socket and femoral stem with a cobalt-chromium alloy femoral head and a polyethylene liner. The patient remained physically active with an exercise routine consisting of walking, swimming, and weight training.

The patient’s orthopedic history was notable for a right knee arthroscopy for intervention due to a torn medial and lateral meniscus, and birth history was noteworthy for a breech presentation. The physical exam was unremarkable except for a slight leg length discrepancy, but the patient did not exhibit a Trendelenburg gait.

Plain X-rays and a computed tomography (CT) scan showed eccentric PE wear and superior migration of the femoral head, which was indicative of significant PE liner wear. No significant osteolysis or periprosthetic loosening was observed on the X-rays or CT scan. He was advised that a hip revision procedure would need to be done, optimally, within the next 6 months to a year.

Discussion

Hip dysplasia represents a broad group of disorders and generally means abnormal development of the hip joint. The term is most commonly used to refer to DDH with inadequate coverage of the femoral head. In one study, 25% of hip replacements performed in patients aged ≤ 40 years were due to underlying hip dysplasia.⁷

Developmental dysplasia of the hip occurs more often in children who present in the breech position.⁸ One theory argues that packaging issues in utero may account for the increased incidence of DDH.⁹ The earliest recorded attempts at hip replacement occurred in Germany, in 1891, when ivory was used to replace the femoral heads of patients whose hip joints had been destroyed by tuberculosis.¹

The orthopedic surgeon Sir John Charnley, who worked at the Manchester Royal Infirmary, is considered the father of the modern THA.¹ His low friction arthroplasty, designed in the early 1960s is identical, in principle, to the M-on-PE prosthesis used today.¹ The PE liner used was ultrahigh molecular weight polyethylene (UHMWPE).¹

Due to the early success of the Charnley prosthesis, the M-on-PE prosthesis became the most widely used. Although PE is the most studied and understood of all acetabular liner materials, it will eventually wear and shed debris. Acetabular cup wear is the most frequent reason for mid-to-long-term revisions, especially in young and active patients.¹⁰ More active patients shed more debris.³ The PE debris instigates the release of inflammatory mediators, which results in chronic inflammation and tissue damage that erodes the supporting bone and can lead to implant loosening or fracture.⁶ Ongoing studies seek to optimize and improve properties of the UHMWPE and to develop alternative bearings. After FDA approval in 1999, highly cross-linked polyethylene liners (HXLPE) rapidly became the standard of care for THAs, at least in the U.S.¹¹ Highly cross-linked polyethylene liners are created from UHMWPE through a process of cross-linking by exposure to gamma radiation, and subsequent heat treatment to neutralize free radicals and limit oxidative degradation.¹²

In one study, the 5-year annual linear wear rate for a HXLPE liner was only 45% of that seen with the UHMWPE liner, although the qualitative wear pattern was the same.¹³ In a study that followed patients for 7 years postoperatively, the mean steady-state wear rate of the HXLPE was 0.005 mm/y compared with 0.037 mm/y for UHMWPE.¹⁴ In a long-term study (a minimum follow-up of 10 years) of 50 patients who were aged < 50 years and underwent THA using HXLPE liners, there was no radiographic evidence of osteolysis or component loosening, and liner wear was 0.020 ± 0.0047 mm/y.¹² In 2005, second-generation HXLPE liners were introduced clinically and have been shown to further reduce wear in vitro compared with both UHMWPE and first-generation HXLPE liners. Callary and colleagues calculated that the wear rates between 1 year and 5 years were all < 0.001 mm/y.¹⁵

The use of ceramic for THAs began in 1970, and ceramic heads on polyethylene (C-on-PE) liners and ceramic-on-ceramic (C-on-C) bearings have been in continual use for > 30 years in Europe. Premarket FDA approval based on European data was granted in 1983; however, the manufacturer voluntarily removed it from the market because of a high incidence of stem loosening (> 30% within 3 years in some series).¹⁶ FDA approvals came much later for C-on-PE (1989) and C-on-C (2003) bearings.

Ceramic is the hardest implant material used, and it can be concluded from many clinical and laboratory reports that C-on-PE and C-on-C combinations confer a potentially significant reduction in wear on THA bearings.¹⁶ Ceramic hips initially had 2 concerns: catastrophic shattering and squeaking. Current ceramic hips have been substantially improved, and some experts feel shattering has been essentially eliminated.¹⁶ Other experts note that ceramic brittleness remains a major concern.¹⁷ Squeaking remains a problem for some, but it usually abates over time. No study has correlated squeaking with impending failure or increased pain or disability.

While C-on-C bearings are now felt to be a good implant for young active patients, these bearings have generally not resulted in significantly lower wear rates and fewer revisions.¹⁸ High rates of wear and osteolysis have been sporadically documented over the 35-year history of ceramic implants.¹⁶ The FDA approved the first ceramic-on-metal total hip replacement system on June 13, 2011.

Metal-on-metal (M-on-M) implants have been used by some for decades, although they were not approved by the FDA until the late 1990s. However, some device recalls have brought negative attention to M-on-M implants.¹⁹ It was felt that they would generate less wear debris than PE, but reports of pseudotumors (from inflammatory mediators) and metallosis have significantly tempered enthusiasm for these products.^20,21 The wear rates are very low, estimated to be only 0.01 mm/y, but concerns about the carcinogenetic potential of systemically increased metal ions remains a possible and much debated concern.^19,22,23 In January 2013, FDA issued a safety communication on M-on-M implants.

Many experts feel that modern ceramic or metal on second-generation HXLPE represents the gold standard and the most predictable bearing choice for young, active patients.¹⁸ Others feel that the optimal choice of bearing surfaces in THA, particularly in the younger and more active patient, remains controversial.²⁴

Follow-Up

Intermittent orthopedic monitoring is recommended for all patients who have undergone a THA. The frequency of hip X-rays on follow-up appointments is left to the orthopedic surgeon. After the initial recovery, serial images every 2 to 5 years can identify progressive failure, and annual X-rays may be used for closer follow-up in high-risk patients.

Patients who experience dislocations, fractures, infections, or pain usually maintain close orthopedic follow-up. Significant wear of the prosthesis damages the socket; osteolysis can cause irreversible bone loss, fracture, and loosening. Massive acetabular bone loss is very difficult to reverse and creates major reconstruction challenges.

Figure 1A is a 2009 X-ray of a woman aged 44 years who underwent a THA after a motor vehicle accident in 1997 and who was advised to have a revision THA when seen in 2009.

Figure 3A is an X-ray of a man aged 71 years who had undergone THA 21 years earlier and had complied with routine follow-up. When his X-rays showed significant wear of the liner and some osteolysis, he was able to undergo a simple revision (Figure 3B).

Three-dimensional CT is useful for quantifying the presence and severity of osteolytic lesions, because plain radiographs may underestimate the amount of bone loss that is present.²⁵ The CT in Figure 3C shows the magnitude of osteolysis that was underestimated by the preoperative plain X-rays (Figure 3A). Computed tomography scans are crucial for surgical planning in the setting of severe acetabular bone loss.

There is a wide spectrum of signs and symptoms that can occur in the setting of acetabular component failure. Pain is a common presenting symptom. Groin pain can represent acetabular failure; thigh pain may be correlated to femoral component failure.²⁵ The clinical patient presentation ultimately depends on the underlying cause: an infection, polyethylene wear, instability, or aseptic loosening.²⁵ Leg-length discrepancy, joint deformity, location of prior incisions, functional status, and baseline neurologic status should be evaluated and documented during the preoperative evaluation as well.²⁵

Case Study Revision Options

The X-rays and CT scans for this case study patient showed that he was a possible candidate for the simplest revision surgery; an isolated liner exchange and replacement of the femoral head. When the original surgery was performed (1997), the only FDA approved PE liner was UHMWPE. To justify isolated liner exchange, the modular acetabular metallic shell also should be well-fixed and appropriately oriented.²⁶ This is evaluated both preoperatively and intraoperatively.

If found to be well fixed with an appropriate orientation and locking mechanism, the UHMWPE liner could be replaced with a HXLPE liner and a larger metal femoral head for improved wear and stability. Acetabular revision is indicted for an asymptomatic patient who has progressive osteolysis, severe wear, or bone loss that would compromise future reconstruction.

Conclusions

Over the past several decades, THA has become recognized as an effective treatment option for the reduction of pain and disability associated with hip joint disease and is associated with successful clinical outcomes. The most frequently noted recommendations for trying to increase the life expectancy of an artificial hip replacement include maintaining a normal weight, keeping leg muscles strong, and avoiding repetitive squatting and kneeling.

As the number of primary THAs has increased and the average age of those undergoing a primary THA has decreased, the need for revisions has risen. Reviews have demonstrated that the most common causes for early total hip revision, regardless of component, included infection, instability/dislocation, and fracture, whereas wear is the most common reason for mid to late revisions.

The wear of all materials used has been shown to be greatest in the most active patients.

Studies continue to identify ways to potentially prevent or reverse osteolysis from wear debris. Alendronate therapy has been shown to prevent and treat PE debris-induced periprosthetic bone loss in rats.²⁷ It also was successfully used in a case report of an asymptomatic woman aged 39 years who had rapid PE wear and aggressive periprosthetic osteolysis within just 2 years of a bilateral THA.²⁸ Other areas of research on decreasing osteolysis in THA recipients include trials with mesenchymal stem cells, bone morphogenic proteins, and gene therapy.⁶

In the U.S., 46,000 revisions were performed in 2004 and this number is expected to more than double by 2030.⁴ Primary care providers are sure to encounter patients who will be in need of a hip revision procedure. It’s important for them to make sure that their patients who have undergone a THA are periodically seen for orthopedic follow-up. Despite the long history of primary THAs, there is still not a single technique and material to suit all patient characteristics.¹ Unfortunately, the same currently applies to hip revision procedures.

Total hip arthroplasty (THA) is considered to be one of the most successful orthopedic interventions of its generation.¹ In 2010, 332,000 THAs were performed in the U.S.² Although used to correct advanced joint diseases in the elderly, the THA procedure has become increasingly common in a younger population for posttraumatic fractures and conditions that lead to early onset secondary arthritis such as avascular necrosis, juvenile rheumatoid arthritis, hip dysplasia, Perthes disease, and femoro-acetabular impingement.

Current hip replacements are expected to function at least 10 to 20 years in 90% of patients.³ As increasing numbers of young patients have these procedures and as seniors continue to live longer, patients will outlast their implants. Younger and more active patients have a higher rate of revision, because the longevity of the prosthesis is usually a function of usage.³ The number of revision THAs is projected to increase 137% by 2030.⁴

Hip resurfacing has been developed as a bone preserving surgical alternative to THA. The first system for use in the U.S. received FDA approval in 2006, but concerns about the metal on metal bearing surfaces, high failure and revision rates, and early catastrophic modes of failure compared with THAs has resulted in the recall of many of these devices. Hip resurfacing may offer some advantages compared with those of a THA in a carefully selected population, but its use will not be further discussed in this case study.⁵ Periprosthetic osteolysis and aseptic loosening are 2 of the long-term consequences of THA.⁶ Bone loss is felt to be secondary to a biologic reaction to particulate debris from implants.⁶ Some patients, especially those with loosening, complete wear, or fracture, will be symptomatic with pain. However, wear and osteolysis is a silent disease unless there is mechanical failure. Other patients may not experience discomfort. Radiographic studies may reveal significant changes, which warrant the recommendation for a hip revision.

Hip revision surgery has 3 major purposes: relieving pain in the affected joint, restoring the patient’s mobility, and removing a loose or damaged prosthesis before irreversible harm is done to the joint. It’s anticipated that most primary care providers (PCPs) will encounter patients who seek advice on the need for a revision hip arthroplasty.

This case will present an asymptomatic patient who underwent a THA in 1997 at age 37, to address developmental dysplasia of the hip (DDH) and was advised to undergo a revision hip arthroplasty due to abnormal radiographic findings at age 55 years. A discussion will follow that includes a brief review of the history of THA, the materials and bearings commonly used, the presenting symptoms or radiographic changes that signal the need for a revision, and the current options available for a patient such as this.

Case Report

A man aged 55 years presented to a new orthopedic surgeon for his first orthopedic appointment in 10 years. The patient had a left metal-on-polyethylene (M-on-PE) THA 18 years prior due to early onset secondary degenerative joint disease from DDH. The patient’s M-on-PE THA was a titanium acetabular socket and femoral stem with a cobalt-chromium alloy femoral head and a polyethylene liner. The patient remained physically active with an exercise routine consisting of walking, swimming, and weight training.

The patient’s orthopedic history was notable for a right knee arthroscopy for intervention due to a torn medial and lateral meniscus, and birth history was noteworthy for a breech presentation. The physical exam was unremarkable except for a slight leg length discrepancy, but the patient did not exhibit a Trendelenburg gait.

Plain X-rays and a computed tomography (CT) scan showed eccentric PE wear and superior migration of the femoral head, which was indicative of significant PE liner wear. No significant osteolysis or periprosthetic loosening was observed on the X-rays or CT scan. He was advised that a hip revision procedure would need to be done, optimally, within the next 6 months to a year.

Discussion

Hip dysplasia represents a broad group of disorders and generally means abnormal development of the hip joint. The term is most commonly used to refer to DDH with inadequate coverage of the femoral head. In one study, 25% of hip replacements performed in patients aged ≤ 40 years were due to underlying hip dysplasia.⁷

Developmental dysplasia of the hip occurs more often in children who present in the breech position.⁸ One theory argues that packaging issues in utero may account for the increased incidence of DDH.⁹ The earliest recorded attempts at hip replacement occurred in Germany, in 1891, when ivory was used to replace the femoral heads of patients whose hip joints had been destroyed by tuberculosis.¹

The orthopedic surgeon Sir John Charnley, who worked at the Manchester Royal Infirmary, is considered the father of the modern THA.¹ His low friction arthroplasty, designed in the early 1960s is identical, in principle, to the M-on-PE prosthesis used today.¹ The PE liner used was ultrahigh molecular weight polyethylene (UHMWPE).¹

Due to the early success of the Charnley prosthesis, the M-on-PE prosthesis became the most widely used. Although PE is the most studied and understood of all acetabular liner materials, it will eventually wear and shed debris. Acetabular cup wear is the most frequent reason for mid-to-long-term revisions, especially in young and active patients.¹⁰ More active patients shed more debris.³ The PE debris instigates the release of inflammatory mediators, which results in chronic inflammation and tissue damage that erodes the supporting bone and can lead to implant loosening or fracture.⁶ Ongoing studies seek to optimize and improve properties of the UHMWPE and to develop alternative bearings. After FDA approval in 1999, highly cross-linked polyethylene liners (HXLPE) rapidly became the standard of care for THAs, at least in the U.S.¹¹ Highly cross-linked polyethylene liners are created from UHMWPE through a process of cross-linking by exposure to gamma radiation, and subsequent heat treatment to neutralize free radicals and limit oxidative degradation.¹²

In one study, the 5-year annual linear wear rate for a HXLPE liner was only 45% of that seen with the UHMWPE liner, although the qualitative wear pattern was the same.¹³ In a study that followed patients for 7 years postoperatively, the mean steady-state wear rate of the HXLPE was 0.005 mm/y compared with 0.037 mm/y for UHMWPE.¹⁴ In a long-term study (a minimum follow-up of 10 years) of 50 patients who were aged < 50 years and underwent THA using HXLPE liners, there was no radiographic evidence of osteolysis or component loosening, and liner wear was 0.020 ± 0.0047 mm/y.¹² In 2005, second-generation HXLPE liners were introduced clinically and have been shown to further reduce wear in vitro compared with both UHMWPE and first-generation HXLPE liners. Callary and colleagues calculated that the wear rates between 1 year and 5 years were all < 0.001 mm/y.¹⁵

The use of ceramic for THAs began in 1970, and ceramic heads on polyethylene (C-on-PE) liners and ceramic-on-ceramic (C-on-C) bearings have been in continual use for > 30 years in Europe. Premarket FDA approval based on European data was granted in 1983; however, the manufacturer voluntarily removed it from the market because of a high incidence of stem loosening (> 30% within 3 years in some series).¹⁶ FDA approvals came much later for C-on-PE (1989) and C-on-C (2003) bearings.

Ceramic is the hardest implant material used, and it can be concluded from many clinical and laboratory reports that C-on-PE and C-on-C combinations confer a potentially significant reduction in wear on THA bearings.¹⁶ Ceramic hips initially had 2 concerns: catastrophic shattering and squeaking. Current ceramic hips have been substantially improved, and some experts feel shattering has been essentially eliminated.¹⁶ Other experts note that ceramic brittleness remains a major concern.¹⁷ Squeaking remains a problem for some, but it usually abates over time. No study has correlated squeaking with impending failure or increased pain or disability.

While C-on-C bearings are now felt to be a good implant for young active patients, these bearings have generally not resulted in significantly lower wear rates and fewer revisions.¹⁸ High rates of wear and osteolysis have been sporadically documented over the 35-year history of ceramic implants.¹⁶ The FDA approved the first ceramic-on-metal total hip replacement system on June 13, 2011.

Metal-on-metal (M-on-M) implants have been used by some for decades, although they were not approved by the FDA until the late 1990s. However, some device recalls have brought negative attention to M-on-M implants.¹⁹ It was felt that they would generate less wear debris than PE, but reports of pseudotumors (from inflammatory mediators) and metallosis have significantly tempered enthusiasm for these products.^20,21 The wear rates are very low, estimated to be only 0.01 mm/y, but concerns about the carcinogenetic potential of systemically increased metal ions remains a possible and much debated concern.^19,22,23 In January 2013, FDA issued a safety communication on M-on-M implants.

Many experts feel that modern ceramic or metal on second-generation HXLPE represents the gold standard and the most predictable bearing choice for young, active patients.¹⁸ Others feel that the optimal choice of bearing surfaces in THA, particularly in the younger and more active patient, remains controversial.²⁴

Follow-Up

Intermittent orthopedic monitoring is recommended for all patients who have undergone a THA. The frequency of hip X-rays on follow-up appointments is left to the orthopedic surgeon. After the initial recovery, serial images every 2 to 5 years can identify progressive failure, and annual X-rays may be used for closer follow-up in high-risk patients.

Patients who experience dislocations, fractures, infections, or pain usually maintain close orthopedic follow-up. Significant wear of the prosthesis damages the socket; osteolysis can cause irreversible bone loss, fracture, and loosening. Massive acetabular bone loss is very difficult to reverse and creates major reconstruction challenges.

Figure 1A is a 2009 X-ray of a woman aged 44 years who underwent a THA after a motor vehicle accident in 1997 and who was advised to have a revision THA when seen in 2009.

Figure 3A is an X-ray of a man aged 71 years who had undergone THA 21 years earlier and had complied with routine follow-up. When his X-rays showed significant wear of the liner and some osteolysis, he was able to undergo a simple revision (Figure 3B).

Three-dimensional CT is useful for quantifying the presence and severity of osteolytic lesions, because plain radiographs may underestimate the amount of bone loss that is present.²⁵ The CT in Figure 3C shows the magnitude of osteolysis that was underestimated by the preoperative plain X-rays (Figure 3A). Computed tomography scans are crucial for surgical planning in the setting of severe acetabular bone loss.

There is a wide spectrum of signs and symptoms that can occur in the setting of acetabular component failure. Pain is a common presenting symptom. Groin pain can represent acetabular failure; thigh pain may be correlated to femoral component failure.²⁵ The clinical patient presentation ultimately depends on the underlying cause: an infection, polyethylene wear, instability, or aseptic loosening.²⁵ Leg-length discrepancy, joint deformity, location of prior incisions, functional status, and baseline neurologic status should be evaluated and documented during the preoperative evaluation as well.²⁵

Case Study Revision Options

The X-rays and CT scans for this case study patient showed that he was a possible candidate for the simplest revision surgery; an isolated liner exchange and replacement of the femoral head. When the original surgery was performed (1997), the only FDA approved PE liner was UHMWPE. To justify isolated liner exchange, the modular acetabular metallic shell also should be well-fixed and appropriately oriented.²⁶ This is evaluated both preoperatively and intraoperatively.

If found to be well fixed with an appropriate orientation and locking mechanism, the UHMWPE liner could be replaced with a HXLPE liner and a larger metal femoral head for improved wear and stability. Acetabular revision is indicted for an asymptomatic patient who has progressive osteolysis, severe wear, or bone loss that would compromise future reconstruction.

Conclusions

Over the past several decades, THA has become recognized as an effective treatment option for the reduction of pain and disability associated with hip joint disease and is associated with successful clinical outcomes. The most frequently noted recommendations for trying to increase the life expectancy of an artificial hip replacement include maintaining a normal weight, keeping leg muscles strong, and avoiding repetitive squatting and kneeling.

As the number of primary THAs has increased and the average age of those undergoing a primary THA has decreased, the need for revisions has risen. Reviews have demonstrated that the most common causes for early total hip revision, regardless of component, included infection, instability/dislocation, and fracture, whereas wear is the most common reason for mid to late revisions.

The wear of all materials used has been shown to be greatest in the most active patients.

Studies continue to identify ways to potentially prevent or reverse osteolysis from wear debris. Alendronate therapy has been shown to prevent and treat PE debris-induced periprosthetic bone loss in rats.²⁷ It also was successfully used in a case report of an asymptomatic woman aged 39 years who had rapid PE wear and aggressive periprosthetic osteolysis within just 2 years of a bilateral THA.²⁸ Other areas of research on decreasing osteolysis in THA recipients include trials with mesenchymal stem cells, bone morphogenic proteins, and gene therapy.⁶

In the U.S., 46,000 revisions were performed in 2004 and this number is expected to more than double by 2030.⁴ Primary care providers are sure to encounter patients who will be in need of a hip revision procedure. It’s important for them to make sure that their patients who have undergone a THA are periodically seen for orthopedic follow-up. Despite the long history of primary THAs, there is still not a single technique and material to suit all patient characteristics.¹ Unfortunately, the same currently applies to hip revision procedures.

Total hip arthroplasty (THA) is considered to be one of the most successful orthopedic interventions of its generation.¹ In 2010, 332,000 THAs were performed in the U.S.² Although used to correct advanced joint diseases in the elderly, the THA procedure has become increasingly common in a younger population for posttraumatic fractures and conditions that lead to early onset secondary arthritis such as avascular necrosis, juvenile rheumatoid arthritis, hip dysplasia, Perthes disease, and femoro-acetabular impingement.

Current hip replacements are expected to function at least 10 to 20 years in 90% of patients.³ As increasing numbers of young patients have these procedures and as seniors continue to live longer, patients will outlast their implants. Younger and more active patients have a higher rate of revision, because the longevity of the prosthesis is usually a function of usage.³ The number of revision THAs is projected to increase 137% by 2030.⁴

Hip resurfacing has been developed as a bone preserving surgical alternative to THA. The first system for use in the U.S. received FDA approval in 2006, but concerns about the metal on metal bearing surfaces, high failure and revision rates, and early catastrophic modes of failure compared with THAs has resulted in the recall of many of these devices. Hip resurfacing may offer some advantages compared with those of a THA in a carefully selected population, but its use will not be further discussed in this case study.⁵ Periprosthetic osteolysis and aseptic loosening are 2 of the long-term consequences of THA.⁶ Bone loss is felt to be secondary to a biologic reaction to particulate debris from implants.⁶ Some patients, especially those with loosening, complete wear, or fracture, will be symptomatic with pain. However, wear and osteolysis is a silent disease unless there is mechanical failure. Other patients may not experience discomfort. Radiographic studies may reveal significant changes, which warrant the recommendation for a hip revision.

Hip revision surgery has 3 major purposes: relieving pain in the affected joint, restoring the patient’s mobility, and removing a loose or damaged prosthesis before irreversible harm is done to the joint. It’s anticipated that most primary care providers (PCPs) will encounter patients who seek advice on the need for a revision hip arthroplasty.

This case will present an asymptomatic patient who underwent a THA in 1997 at age 37, to address developmental dysplasia of the hip (DDH) and was advised to undergo a revision hip arthroplasty due to abnormal radiographic findings at age 55 years. A discussion will follow that includes a brief review of the history of THA, the materials and bearings commonly used, the presenting symptoms or radiographic changes that signal the need for a revision, and the current options available for a patient such as this.

Case Report

A man aged 55 years presented to a new orthopedic surgeon for his first orthopedic appointment in 10 years. The patient had a left metal-on-polyethylene (M-on-PE) THA 18 years prior due to early onset secondary degenerative joint disease from DDH. The patient’s M-on-PE THA was a titanium acetabular socket and femoral stem with a cobalt-chromium alloy femoral head and a polyethylene liner. The patient remained physically active with an exercise routine consisting of walking, swimming, and weight training.

The patient’s orthopedic history was notable for a right knee arthroscopy for intervention due to a torn medial and lateral meniscus, and birth history was noteworthy for a breech presentation. The physical exam was unremarkable except for a slight leg length discrepancy, but the patient did not exhibit a Trendelenburg gait.

Plain X-rays and a computed tomography (CT) scan showed eccentric PE wear and superior migration of the femoral head, which was indicative of significant PE liner wear. No significant osteolysis or periprosthetic loosening was observed on the X-rays or CT scan. He was advised that a hip revision procedure would need to be done, optimally, within the next 6 months to a year.

Discussion

Hip dysplasia represents a broad group of disorders and generally means abnormal development of the hip joint. The term is most commonly used to refer to DDH with inadequate coverage of the femoral head. In one study, 25% of hip replacements performed in patients aged ≤ 40 years were due to underlying hip dysplasia.⁷

Developmental dysplasia of the hip occurs more often in children who present in the breech position.⁸ One theory argues that packaging issues in utero may account for the increased incidence of DDH.⁹ The earliest recorded attempts at hip replacement occurred in Germany, in 1891, when ivory was used to replace the femoral heads of patients whose hip joints had been destroyed by tuberculosis.¹

The orthopedic surgeon Sir John Charnley, who worked at the Manchester Royal Infirmary, is considered the father of the modern THA.¹ His low friction arthroplasty, designed in the early 1960s is identical, in principle, to the M-on-PE prosthesis used today.¹ The PE liner used was ultrahigh molecular weight polyethylene (UHMWPE).¹

Due to the early success of the Charnley prosthesis, the M-on-PE prosthesis became the most widely used. Although PE is the most studied and understood of all acetabular liner materials, it will eventually wear and shed debris. Acetabular cup wear is the most frequent reason for mid-to-long-term revisions, especially in young and active patients.¹⁰ More active patients shed more debris.³ The PE debris instigates the release of inflammatory mediators, which results in chronic inflammation and tissue damage that erodes the supporting bone and can lead to implant loosening or fracture.⁶ Ongoing studies seek to optimize and improve properties of the UHMWPE and to develop alternative bearings. After FDA approval in 1999, highly cross-linked polyethylene liners (HXLPE) rapidly became the standard of care for THAs, at least in the U.S.¹¹ Highly cross-linked polyethylene liners are created from UHMWPE through a process of cross-linking by exposure to gamma radiation, and subsequent heat treatment to neutralize free radicals and limit oxidative degradation.¹²

In one study, the 5-year annual linear wear rate for a HXLPE liner was only 45% of that seen with the UHMWPE liner, although the qualitative wear pattern was the same.¹³ In a study that followed patients for 7 years postoperatively, the mean steady-state wear rate of the HXLPE was 0.005 mm/y compared with 0.037 mm/y for UHMWPE.¹⁴ In a long-term study (a minimum follow-up of 10 years) of 50 patients who were aged < 50 years and underwent THA using HXLPE liners, there was no radiographic evidence of osteolysis or component loosening, and liner wear was 0.020 ± 0.0047 mm/y.¹² In 2005, second-generation HXLPE liners were introduced clinically and have been shown to further reduce wear in vitro compared with both UHMWPE and first-generation HXLPE liners. Callary and colleagues calculated that the wear rates between 1 year and 5 years were all < 0.001 mm/y.¹⁵

The use of ceramic for THAs began in 1970, and ceramic heads on polyethylene (C-on-PE) liners and ceramic-on-ceramic (C-on-C) bearings have been in continual use for > 30 years in Europe. Premarket FDA approval based on European data was granted in 1983; however, the manufacturer voluntarily removed it from the market because of a high incidence of stem loosening (> 30% within 3 years in some series).¹⁶ FDA approvals came much later for C-on-PE (1989) and C-on-C (2003) bearings.

Ceramic is the hardest implant material used, and it can be concluded from many clinical and laboratory reports that C-on-PE and C-on-C combinations confer a potentially significant reduction in wear on THA bearings.¹⁶ Ceramic hips initially had 2 concerns: catastrophic shattering and squeaking. Current ceramic hips have been substantially improved, and some experts feel shattering has been essentially eliminated.¹⁶ Other experts note that ceramic brittleness remains a major concern.¹⁷ Squeaking remains a problem for some, but it usually abates over time. No study has correlated squeaking with impending failure or increased pain or disability.

While C-on-C bearings are now felt to be a good implant for young active patients, these bearings have generally not resulted in significantly lower wear rates and fewer revisions.¹⁸ High rates of wear and osteolysis have been sporadically documented over the 35-year history of ceramic implants.¹⁶ The FDA approved the first ceramic-on-metal total hip replacement system on June 13, 2011.

Metal-on-metal (M-on-M) implants have been used by some for decades, although they were not approved by the FDA until the late 1990s. However, some device recalls have brought negative attention to M-on-M implants.¹⁹ It was felt that they would generate less wear debris than PE, but reports of pseudotumors (from inflammatory mediators) and metallosis have significantly tempered enthusiasm for these products.^20,21 The wear rates are very low, estimated to be only 0.01 mm/y, but concerns about the carcinogenetic potential of systemically increased metal ions remains a possible and much debated concern.^19,22,23 In January 2013, FDA issued a safety communication on M-on-M implants.

Many experts feel that modern ceramic or metal on second-generation HXLPE represents the gold standard and the most predictable bearing choice for young, active patients.¹⁸ Others feel that the optimal choice of bearing surfaces in THA, particularly in the younger and more active patient, remains controversial.²⁴

Follow-Up

Intermittent orthopedic monitoring is recommended for all patients who have undergone a THA. The frequency of hip X-rays on follow-up appointments is left to the orthopedic surgeon. After the initial recovery, serial images every 2 to 5 years can identify progressive failure, and annual X-rays may be used for closer follow-up in high-risk patients.

Patients who experience dislocations, fractures, infections, or pain usually maintain close orthopedic follow-up. Significant wear of the prosthesis damages the socket; osteolysis can cause irreversible bone loss, fracture, and loosening. Massive acetabular bone loss is very difficult to reverse and creates major reconstruction challenges.

Figure 1A is a 2009 X-ray of a woman aged 44 years who underwent a THA after a motor vehicle accident in 1997 and who was advised to have a revision THA when seen in 2009.

Figure 3A is an X-ray of a man aged 71 years who had undergone THA 21 years earlier and had complied with routine follow-up. When his X-rays showed significant wear of the liner and some osteolysis, he was able to undergo a simple revision (Figure 3B).

Three-dimensional CT is useful for quantifying the presence and severity of osteolytic lesions, because plain radiographs may underestimate the amount of bone loss that is present.²⁵ The CT in Figure 3C shows the magnitude of osteolysis that was underestimated by the preoperative plain X-rays (Figure 3A). Computed tomography scans are crucial for surgical planning in the setting of severe acetabular bone loss.

There is a wide spectrum of signs and symptoms that can occur in the setting of acetabular component failure. Pain is a common presenting symptom. Groin pain can represent acetabular failure; thigh pain may be correlated to femoral component failure.²⁵ The clinical patient presentation ultimately depends on the underlying cause: an infection, polyethylene wear, instability, or aseptic loosening.²⁵ Leg-length discrepancy, joint deformity, location of prior incisions, functional status, and baseline neurologic status should be evaluated and documented during the preoperative evaluation as well.²⁵

Case Study Revision Options

The X-rays and CT scans for this case study patient showed that he was a possible candidate for the simplest revision surgery; an isolated liner exchange and replacement of the femoral head. When the original surgery was performed (1997), the only FDA approved PE liner was UHMWPE. To justify isolated liner exchange, the modular acetabular metallic shell also should be well-fixed and appropriately oriented.²⁶ This is evaluated both preoperatively and intraoperatively.

If found to be well fixed with an appropriate orientation and locking mechanism, the UHMWPE liner could be replaced with a HXLPE liner and a larger metal femoral head for improved wear and stability. Acetabular revision is indicted for an asymptomatic patient who has progressive osteolysis, severe wear, or bone loss that would compromise future reconstruction.

Conclusions

Over the past several decades, THA has become recognized as an effective treatment option for the reduction of pain and disability associated with hip joint disease and is associated with successful clinical outcomes. The most frequently noted recommendations for trying to increase the life expectancy of an artificial hip replacement include maintaining a normal weight, keeping leg muscles strong, and avoiding repetitive squatting and kneeling.

As the number of primary THAs has increased and the average age of those undergoing a primary THA has decreased, the need for revisions has risen. Reviews have demonstrated that the most common causes for early total hip revision, regardless of component, included infection, instability/dislocation, and fracture, whereas wear is the most common reason for mid to late revisions.

The wear of all materials used has been shown to be greatest in the most active patients.

Studies continue to identify ways to potentially prevent or reverse osteolysis from wear debris. Alendronate therapy has been shown to prevent and treat PE debris-induced periprosthetic bone loss in rats.²⁷ It also was successfully used in a case report of an asymptomatic woman aged 39 years who had rapid PE wear and aggressive periprosthetic osteolysis within just 2 years of a bilateral THA.²⁸ Other areas of research on decreasing osteolysis in THA recipients include trials with mesenchymal stem cells, bone morphogenic proteins, and gene therapy.⁶

In the U.S., 46,000 revisions were performed in 2004 and this number is expected to more than double by 2030.⁴ Primary care providers are sure to encounter patients who will be in need of a hip revision procedure. It’s important for them to make sure that their patients who have undergone a THA are periodically seen for orthopedic follow-up. Despite the long history of primary THAs, there is still not a single technique and material to suit all patient characteristics.¹ Unfortunately, the same currently applies to hip revision procedures.