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HIV Infection and Avascular Necrosis
Case Report JANAC Vol. 12, No. 5, September/October 2001 Savini, James / HIV and Avascular Necrosis
HIV Infection and Avascular Necrosis Carolyn J. Savini, FNP Christopher W. James, PharmD
As HIV disease has become a chronic illness, clinicians are faced with dilemmas and conditions that are often unfamiliar to both our patients’ lives and our clinical expertise. Recently, in a review of the literature, we discovered the impact that highly active antiretroviral therapy (HAART) may have on multiple organ systems, including musculoskeletal adverse effects, specifically avascular necrosis (AVN) (Plate & Boyle, 2000). Clinicians who care for clients receiving HAART need to be aware of the impact of AVN and be able to recognize the presenting symptoms. We would like to share the clinical experience of one of our clients who was diagnosed with AVN. This client has been treated for HIV for the past 6 years with varied immunologic/virologic results. He has received multiple medication regimens for his HIV disease and has other contributing factors for AVN. This makes the certainty of the cause of this diagnosis of AVN difficult. However, HAART remains a distinct possible cause for this client’s AVN.
Clinical Presentation A 54-year-old HIV-positive male presented to our HIV outpatient clinic with complaints of right groin pain. The patient stated he was decorating his store window for the holidays when he fell from a stool and “pulled his groin muscle.” He was noticed to be limping from the waiting room to the examination room. The patient reported that the joint pain did not occur until after he had sustained the fall. Antiretroviral medications at the time of presentation included stavudine 40 mg twice daily, lamivudine 150 mg twice daily, and nelfinavir 1,250 mg twice daily. He has received this current combination for
approximately 4 years. Other medications included trimethoprim/sulfamethoxazole 1 double-strength tablet daily, acyclovir 400 mg twice daily, and lansoprazole 30 mg daily. The patient has a history of ankylosing spondylitis with both injectable and oral corticosteroid use for 5 years. In addition, this patient received two “bursts” of oral corticosteroids in 1997 while undergoing treatment for Bell’s palsy. Additional medical history includes cigarette smoking for more than 30 years, a history of alcohol abuse (which subsequently was stopped 6 years ago after learning of his HIV diagnosis), and hypertriglyceridemia, which became evident after 4 years of treatment with HAART. On physical examination, the patient was afebrile, with tenderness upon palpation of the right groin. No palpable inguinal or femoral lymph nodes or masses were noted on examination. In addition, no increased pain was noticed with manipulation of right hip joint. Neurologic examination was within normal limits in the lower extremities. Legs were acyanotic and warm to the touch with good capillary refill bilaterally. In addition, knee joints were stable with manipulation bilaterally. Results of an X ray of the hip were negative for fracture; however, mild osteoarthritis was recognized. The patient was diagnosed with a muscle strain at the insertion site of sartorius muscle. He was instructed to rest the joint and use warm compresses three times daily. He was also prescribed nabumetone 500 mg twice daily. Carolyn J., Savini, FNP, is a clinic coordinator and nurse practitioner at the HIV Wellness Clinic, Georgetown, DE. Christopher W. James, PharmD, is a clinical pharmacist for the HIV Program–Christiana Care Health System, Georgetown, DE.
JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE, Vol. 12, No. 5, September/October 2001, 83-85 Copyright © 2001 Association of Nurses in AIDS Care
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JANAC Vol. 12, No. 5, September/October 2001
Despite the use of anti-inflammatory medications, the patient continued to experience increased pain and decreased mobility of the hip. On his return visit, it was shared with the medical staff that he was using a “TV stand” to aid with ambulation and provide support. Subsequently, he was prescribed oxycodone 5 mg/acetaminophen 325 mg as needed for pain. In addition, an MRI was ordered, which revealed bilateral avascular necrosis of the hip joints. This client presented 2 days following his MRI at the office to review test results and discuss the findings. At this interaction, the client shared with the clinicians the increased pain he was undergoing and the relative ineffectiveness of the oxycodone/acetaminophen. He was subsequently prescribed morphine sulfate 30 mg twice daily. Also, he was encouraged to use the oxycodone/ acetaminophen for breakthrough pain. After results from the MRI were reviewed, this patient was referred to an orthopedic surgeon for evaluation and intervention. The surgeon recommended bilateral decompression of the femoral heads.
Discussion A disruption or cessation of blood supply to a bone can result in death of bone tissue. This death is known as avascular necrosis. It is also known as aseptic necrosis, ischemic bone necrosis, or osteonecrosis (Plate & Boyle, 2000). After the cells die, swelling takes place, which causes increased pressure in the joint. This initiates a vicious cycle whereby increased pressure further impedes circulation, promoting even greater cell death. Joints most commonly affected include the hips, knees, shoulders, wrists, and feet. Avascular necrosis may be directly related to a traumatic or nontraumatic event to the joint (Mitchell et al., 1987). Trauma to the joint includes fractures, injuries, and damage to the vasculature of the bone involved. Nontraumatic events include pancreatitis, alcohol use, tobacco use, long-term corticosteroid use, or hypertriglyceridemia (Mont & Hungerford, 1995; Plate & Boyle, 2000; Wolfe & Taylor-Butler, 2000). Chronic alcohol use or abuse leads to the development of fatty liver, which may produce fat emboli. These fat emboli can lodge in the endarteries that provide blood supply to bones. This may be a precipitating factor in
AVN. Corticosteroids may induce a similar condition through the production of fat emboli and cause increased bone marrow pressure (Mont & Hungerford, 1995; Wolfe & Taylor-Butler, 2000). AVN is related to the total or cumulative corticosteroid dose; however, high doses of corticosteroids have also been implicated (Wolfe & Taylor-Butler, 2000). Megestrol acetate is commonly used to treat AIDS-related wasting. Cases of AVN with this agent have also been reported and were suggested to be secondary to the corticosteroid activity of megestrol acetate (Gibert, Koller, Mann, Bacsanyi, & Malozowski, 1998). Other risk factors or conditions that may also contribute to this disorder include systemic lupus erythematosus, Gaucher disease, and sickle cell anemia (Mont & Hungerford, 1995; Wolfe & Taylor-Butler, 2000). Before 1996, 23 cases of AVN in HIV-infected individuals had been reported in the literature (Timpone, Fluhme, Nascone, Evans, & Kumar, 1999). However, an increasing number of cases have been reported at recent HIV conferences. Plate and Boyle (2000) conducted a comprehensive literature review regarding HAART and its association with AVN. Their study reinforces the appropriateness of considering HAART as a contributing factor when diagnosing AVN. Timpone et al. (1999) identified 8 cases of AVN in a retrospective chart review from June 1997 to May 1998, for an estimated prevalence in their population of 1.33%. Five patients had concomitant risk factors for AVN, including pancreatitis, corticosteroid use, and alcoholism. In addition, 5 patients had elevated triglyceride levels and 1 patient had documented lipodystrophy. The authors suggested an association between protease inhibitors and the increased incidence of AVN and suggested lipodystrophy as the potential pathogenic factor. The mean duration of protease inhibitor therapy prior to the development of symptoms and the diagnosis was 59.7 weeks and 65.6 weeks, respectively (Timpone et al., 1999). Protease inhibitor therapy has previously been associated with decreased bone mineral density (Tebas et al., 2000). However, a definitive association between protease inhibitors and avascular necrosis has not been proven conclusively (Plate & Boyle, 2000). A recent abstract found no association between either protease inhibitor therapy or lipodystrophy and avascular necrosis (Keruly, Chaisson, & Moore,
Savini, James / HIV and Avascular Necrosis
2001). It was previously suggested that AVN in HIV-infected patients may be secondary to the resultant thrombosis that is secondary to anticardiolipin antibody production and/or Protein S deficiency (Rademaker, Dobro, & Solomon, 1997). This client had multiple risk factors for the development of AVN, including corticosteroid use, tobacco use, history of alcohol abuse, hypertriglyceridemia, and the use of HAART. Although it is impossible to specifically state which one of these contributing factors may have caused AVN, it is imperative to remember all possibilities in the evaluation. A number of staging systems have been developed for the classification of AVN. Classification by the staging systems varies, but all incorporate clinical findings and the results of radiography and MRI. This patient’s AVN is best classified as Stage I. Stage I AVN is defined and characterized by positive clinical findings, positive findings from bone scan/MRI, and negative radiographic findings (Mitchell et al., 1987; Steinberg, Hayken, & Steinberg, 1995; Wolfe & TaylorButler, 2000). It is our conclusion that clients who receive HAART and present with complaints of joint pain should be aggressively evaluated for the possibility of AVN. Early recognition and intervention are imperative in the effective management of this painful diagnosis. Clinicians who care for clients with HIV infection may find the mnemonic STAMP helpful when evaluating HIV-infected patients for risk factors associated with the development of AVN. STAMP stands for the following: S = Steroid use T = Tobacco use/triglyceride elevation A = Alcohol/antiretroviral use M = Megestrol acetate use P = Pancreatitis These seven risk factors are the most prevalent in our HIV patient population. Physical symptoms will vary depending on the involved joint. In a client with femoral head involvement, groin pain can be an initial complaint. Clients may present with pain, diminished mobility in the affected joint, or both (Plate & Boyle, 2000). Anti-inflammatory medications may provide initial relief with prompt identification. This, in
85
combination with instructing the client to avoid contributing factors, may potentially decrease the progression of AVN. Beyond this, management options include electrical stimulation, core decompression, and joint replacement (Mont & Hungerford, 1995). All patients with documented AVN should be referred to an orthopedist for appropriate management. Our patient’s AVN will be managed by bilateral core decompression of the femoral heads. This procedure will relieve pressure inside the femoral heads in hope of providing revascularization and blood supply to the femoral bones.
References Gibert, C., Koller, E., Mann, M., Bacsanyi, J., & Malozowski, S. (1998, February). Avascular necrosis in AIDS patients receiving megestrol acetate [Abstract 478]. Abstract presented at the 5th Conference on Retroviruses and Opportunistic Infections, Chicago. Keruly, J. C., Chaisson, R. E., & Moore, R. D. (2001, February). Increasing incidence of avascular necrosis of the hip in HIV-infected patients [Abstract 637]. Abstract presented at the 8th Conference on Retroviruses and Opportunistic Infections, Chicago. Mitchell, D. G., Rao, V. M., Dalinka, M. K., Spritzer, C. E., Alavi, A., Steinberg, M. E., Fallon, M., & Kressel, H. Y. (1987). Femoral head avascular necrosis: Correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings. Radiology, 162, 709-715. Mont, M. A., & Hungerford, D. S. (1995). Non-traumatic avascular necrosis of the femoral head. Journal of Bone and Joint Surgery—American Volume, 77-A, 459-474. Plate, A., & Boyle, B. A. (2000). Review of avascular necrosis and HIV. AIDS Reader, 10, 570-573. Rademaker, J., Dobro, J. S., & Solomon, G. (1997). Osteonecrosis and human immunodeficiency virus infection. Journal of Rheumatology, 24, 601-604. Steinberg, M. E., Hayken, G. D., & Steinberg, D. R. (1995). A quantitative system for staging avascular necrosis. Journal of Bone and Joint Surgery—British Volume, 77-B, 34-41. Tebas, P., Powderly, W. G., Claxton, S., Marin, D., Tantisiri, W., Teitelbaum, S. L., & Yarasheski, K. E. (2000). Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS, 14, F63-F67. Timpone, J., Fluhme, D., Nascone, J., Evans, B., & Kumar, P. (1999, January-February). Avascular necrosis in HIV+ patients: A potential link to protease inhibitors [Abstract 680]. Abstract presented at the 6th Conference on Retroviruses and Opportunistic Infections, Chicago. Wolfe, C. J., & Taylor-Butler, K. L. (2000). Avascular necrosis: a case history and literature review. Archives of Family Medicine, 9, 291-294.
HIV Infection and Avascular Necrosis Carolyn J. Savini, FNP Christopher W. James, PharmD
As HIV disease has become a chronic illness, clinicians are faced with dilemmas and conditions that are often unfamiliar to both our patients’ lives and our clinical expertise. Recently, in a review of the literature, we discovered the impact that highly active antiretroviral therapy (HAART) may have on multiple organ systems, including musculoskeletal adverse effects, specifically avascular necrosis (AVN) (Plate & Boyle, 2000). Clinicians who care for clients receiving HAART need to be aware of the impact of AVN and be able to recognize the presenting symptoms. We would like to share the clinical experience of one of our clients who was diagnosed with AVN. This client has been treated for HIV for the past 6 years with varied immunologic/virologic results. He has received multiple medication regimens for his HIV disease and has other contributing factors for AVN. This makes the certainty of the cause of this diagnosis of AVN difficult. However, HAART remains a distinct possible cause for this client’s AVN.
Clinical Presentation A 54-year-old HIV-positive male presented to our HIV outpatient clinic with complaints of right groin pain. The patient stated he was decorating his store window for the holidays when he fell from a stool and “pulled his groin muscle.” He was noticed to be limping from the waiting room to the examination room. The patient reported that the joint pain did not occur until after he had sustained the fall. Antiretroviral medications at the time of presentation included stavudine 40 mg twice daily, lamivudine 150 mg twice daily, and nelfinavir 1,250 mg twice daily. He has received this current combination for
approximately 4 years. Other medications included trimethoprim/sulfamethoxazole 1 double-strength tablet daily, acyclovir 400 mg twice daily, and lansoprazole 30 mg daily. The patient has a history of ankylosing spondylitis with both injectable and oral corticosteroid use for 5 years. In addition, this patient received two “bursts” of oral corticosteroids in 1997 while undergoing treatment for Bell’s palsy. Additional medical history includes cigarette smoking for more than 30 years, a history of alcohol abuse (which subsequently was stopped 6 years ago after learning of his HIV diagnosis), and hypertriglyceridemia, which became evident after 4 years of treatment with HAART. On physical examination, the patient was afebrile, with tenderness upon palpation of the right groin. No palpable inguinal or femoral lymph nodes or masses were noted on examination. In addition, no increased pain was noticed with manipulation of right hip joint. Neurologic examination was within normal limits in the lower extremities. Legs were acyanotic and warm to the touch with good capillary refill bilaterally. In addition, knee joints were stable with manipulation bilaterally. Results of an X ray of the hip were negative for fracture; however, mild osteoarthritis was recognized. The patient was diagnosed with a muscle strain at the insertion site of sartorius muscle. He was instructed to rest the joint and use warm compresses three times daily. He was also prescribed nabumetone 500 mg twice daily. Carolyn J., Savini, FNP, is a clinic coordinator and nurse practitioner at the HIV Wellness Clinic, Georgetown, DE. Christopher W. James, PharmD, is a clinical pharmacist for the HIV Program–Christiana Care Health System, Georgetown, DE.
JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE, Vol. 12, No. 5, September/October 2001, 83-85 Copyright © 2001 Association of Nurses in AIDS Care
84
JANAC Vol. 12, No. 5, September/October 2001
Despite the use of anti-inflammatory medications, the patient continued to experience increased pain and decreased mobility of the hip. On his return visit, it was shared with the medical staff that he was using a “TV stand” to aid with ambulation and provide support. Subsequently, he was prescribed oxycodone 5 mg/acetaminophen 325 mg as needed for pain. In addition, an MRI was ordered, which revealed bilateral avascular necrosis of the hip joints. This client presented 2 days following his MRI at the office to review test results and discuss the findings. At this interaction, the client shared with the clinicians the increased pain he was undergoing and the relative ineffectiveness of the oxycodone/acetaminophen. He was subsequently prescribed morphine sulfate 30 mg twice daily. Also, he was encouraged to use the oxycodone/ acetaminophen for breakthrough pain. After results from the MRI were reviewed, this patient was referred to an orthopedic surgeon for evaluation and intervention. The surgeon recommended bilateral decompression of the femoral heads.
Discussion A disruption or cessation of blood supply to a bone can result in death of bone tissue. This death is known as avascular necrosis. It is also known as aseptic necrosis, ischemic bone necrosis, or osteonecrosis (Plate & Boyle, 2000). After the cells die, swelling takes place, which causes increased pressure in the joint. This initiates a vicious cycle whereby increased pressure further impedes circulation, promoting even greater cell death. Joints most commonly affected include the hips, knees, shoulders, wrists, and feet. Avascular necrosis may be directly related to a traumatic or nontraumatic event to the joint (Mitchell et al., 1987). Trauma to the joint includes fractures, injuries, and damage to the vasculature of the bone involved. Nontraumatic events include pancreatitis, alcohol use, tobacco use, long-term corticosteroid use, or hypertriglyceridemia (Mont & Hungerford, 1995; Plate & Boyle, 2000; Wolfe & Taylor-Butler, 2000). Chronic alcohol use or abuse leads to the development of fatty liver, which may produce fat emboli. These fat emboli can lodge in the endarteries that provide blood supply to bones. This may be a precipitating factor in
AVN. Corticosteroids may induce a similar condition through the production of fat emboli and cause increased bone marrow pressure (Mont & Hungerford, 1995; Wolfe & Taylor-Butler, 2000). AVN is related to the total or cumulative corticosteroid dose; however, high doses of corticosteroids have also been implicated (Wolfe & Taylor-Butler, 2000). Megestrol acetate is commonly used to treat AIDS-related wasting. Cases of AVN with this agent have also been reported and were suggested to be secondary to the corticosteroid activity of megestrol acetate (Gibert, Koller, Mann, Bacsanyi, & Malozowski, 1998). Other risk factors or conditions that may also contribute to this disorder include systemic lupus erythematosus, Gaucher disease, and sickle cell anemia (Mont & Hungerford, 1995; Wolfe & Taylor-Butler, 2000). Before 1996, 23 cases of AVN in HIV-infected individuals had been reported in the literature (Timpone, Fluhme, Nascone, Evans, & Kumar, 1999). However, an increasing number of cases have been reported at recent HIV conferences. Plate and Boyle (2000) conducted a comprehensive literature review regarding HAART and its association with AVN. Their study reinforces the appropriateness of considering HAART as a contributing factor when diagnosing AVN. Timpone et al. (1999) identified 8 cases of AVN in a retrospective chart review from June 1997 to May 1998, for an estimated prevalence in their population of 1.33%. Five patients had concomitant risk factors for AVN, including pancreatitis, corticosteroid use, and alcoholism. In addition, 5 patients had elevated triglyceride levels and 1 patient had documented lipodystrophy. The authors suggested an association between protease inhibitors and the increased incidence of AVN and suggested lipodystrophy as the potential pathogenic factor. The mean duration of protease inhibitor therapy prior to the development of symptoms and the diagnosis was 59.7 weeks and 65.6 weeks, respectively (Timpone et al., 1999). Protease inhibitor therapy has previously been associated with decreased bone mineral density (Tebas et al., 2000). However, a definitive association between protease inhibitors and avascular necrosis has not been proven conclusively (Plate & Boyle, 2000). A recent abstract found no association between either protease inhibitor therapy or lipodystrophy and avascular necrosis (Keruly, Chaisson, & Moore,
Savini, James / HIV and Avascular Necrosis
2001). It was previously suggested that AVN in HIV-infected patients may be secondary to the resultant thrombosis that is secondary to anticardiolipin antibody production and/or Protein S deficiency (Rademaker, Dobro, & Solomon, 1997). This client had multiple risk factors for the development of AVN, including corticosteroid use, tobacco use, history of alcohol abuse, hypertriglyceridemia, and the use of HAART. Although it is impossible to specifically state which one of these contributing factors may have caused AVN, it is imperative to remember all possibilities in the evaluation. A number of staging systems have been developed for the classification of AVN. Classification by the staging systems varies, but all incorporate clinical findings and the results of radiography and MRI. This patient’s AVN is best classified as Stage I. Stage I AVN is defined and characterized by positive clinical findings, positive findings from bone scan/MRI, and negative radiographic findings (Mitchell et al., 1987; Steinberg, Hayken, & Steinberg, 1995; Wolfe & TaylorButler, 2000). It is our conclusion that clients who receive HAART and present with complaints of joint pain should be aggressively evaluated for the possibility of AVN. Early recognition and intervention are imperative in the effective management of this painful diagnosis. Clinicians who care for clients with HIV infection may find the mnemonic STAMP helpful when evaluating HIV-infected patients for risk factors associated with the development of AVN. STAMP stands for the following: S = Steroid use T = Tobacco use/triglyceride elevation A = Alcohol/antiretroviral use M = Megestrol acetate use P = Pancreatitis These seven risk factors are the most prevalent in our HIV patient population. Physical symptoms will vary depending on the involved joint. In a client with femoral head involvement, groin pain can be an initial complaint. Clients may present with pain, diminished mobility in the affected joint, or both (Plate & Boyle, 2000). Anti-inflammatory medications may provide initial relief with prompt identification. This, in
85
combination with instructing the client to avoid contributing factors, may potentially decrease the progression of AVN. Beyond this, management options include electrical stimulation, core decompression, and joint replacement (Mont & Hungerford, 1995). All patients with documented AVN should be referred to an orthopedist for appropriate management. Our patient’s AVN will be managed by bilateral core decompression of the femoral heads. This procedure will relieve pressure inside the femoral heads in hope of providing revascularization and blood supply to the femoral bones.
References Gibert, C., Koller, E., Mann, M., Bacsanyi, J., & Malozowski, S. (1998, February). Avascular necrosis in AIDS patients receiving megestrol acetate [Abstract 478]. Abstract presented at the 5th Conference on Retroviruses and Opportunistic Infections, Chicago. Keruly, J. C., Chaisson, R. E., & Moore, R. D. (2001, February). Increasing incidence of avascular necrosis of the hip in HIV-infected patients [Abstract 637]. Abstract presented at the 8th Conference on Retroviruses and Opportunistic Infections, Chicago. Mitchell, D. G., Rao, V. M., Dalinka, M. K., Spritzer, C. E., Alavi, A., Steinberg, M. E., Fallon, M., & Kressel, H. Y. (1987). Femoral head avascular necrosis: Correlation of MR imaging, radiographic staging, radionuclide imaging, and clinical findings. Radiology, 162, 709-715. Mont, M. A., & Hungerford, D. S. (1995). Non-traumatic avascular necrosis of the femoral head. Journal of Bone and Joint Surgery—American Volume, 77-A, 459-474. Plate, A., & Boyle, B. A. (2000). Review of avascular necrosis and HIV. AIDS Reader, 10, 570-573. Rademaker, J., Dobro, J. S., & Solomon, G. (1997). Osteonecrosis and human immunodeficiency virus infection. Journal of Rheumatology, 24, 601-604. Steinberg, M. E., Hayken, G. D., & Steinberg, D. R. (1995). A quantitative system for staging avascular necrosis. Journal of Bone and Joint Surgery—British Volume, 77-B, 34-41. Tebas, P., Powderly, W. G., Claxton, S., Marin, D., Tantisiri, W., Teitelbaum, S. L., & Yarasheski, K. E. (2000). Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS, 14, F63-F67. Timpone, J., Fluhme, D., Nascone, J., Evans, B., & Kumar, P. (1999, January-February). Avascular necrosis in HIV+ patients: A potential link to protease inhibitors [Abstract 680]. Abstract presented at the 6th Conference on Retroviruses and Opportunistic Infections, Chicago. Wolfe, C. J., & Taylor-Butler, K. L. (2000). Avascular necrosis: a case history and literature review. Archives of Family Medicine, 9, 291-294.