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HIV Pain Management: Considerations, Ideas & Suggestions

HIV Pain Management: Considerations, Ideas & Suggestions. Barry Eliot Cole, MD, MPA Executive Director, American Society of Pain Educators. Where We Are in 2005. HIV/AIDS pandemic has not ended In US approx. 1 million are HIV-infected 1 in 3 HIV-infected are unaware of diagnosis

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HIV Pain Management: Considerations, Ideas & Suggestions

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  1. HIV Pain Management: Considerations, Ideas & Suggestions Barry Eliot Cole, MD, MPA Executive Director, American Society of Pain Educators

  2. Where We Are in 2005 • HIV/AIDS pandemic has not ended • In US approx. 1 million are HIV-infected • 1 in 3 HIV-infected are unaware of diagnosis • Major AIDS era stages: pre- & post-HAART • People being treated for HIV are now healthier, living otherwise normal lives Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  3. HIV and Pain Overlap • Neuromuscular complications are common • Most common pain problems are • Musculoskeletal • Distal symmetrical polyneuropathy (DIS) • Abdominal pain • Headache • Other neurological problems • Consequences of opportunistic infections Glare PA. Pain in patients with HIV infection: issues for the new millennium. European J Pain 2001; 5 (Suppl A):43-48.

  4. In the Pre-HAART Era • Short life expectancy, so model used was that of cancer patients • Reliance upon the 3-4 step WHO ladder • Expectation for lots of complications Glare PA. Pain in patients with HIV infection: issues for the new millennium. European J Pain 2001; 5 (Suppl A):43-48.

  5. Why Mirror Cancer Pain Therapy? • Was reasonable when large segments of AIDS patients were debilitated and considered to be terminal • Patients surveyed as late as 1998 continued to list pain as being associated with worse perceived health and perceived quality of life Lorenz KA et al, Ann Intern Med 2001; 134: 854.

  6. Post-HAART • Longer life with more “chronicity” • Multiple pains occur • Negative impact on QOL • More psychosocial issues • Use of polypharmacy common • Use of “pyramid plus ribbon” • Less efficacy of treatments than cancer Glare PA. Pain in patients with HIV infection: issues for the new millennium. European J Pain 2001; 5 (Suppl A):43-48.

  7. What About Demanding, Complex Pain Patients? • Drug seekers (addicts and diverters) • Those with special needs • Minorities • Substance abusers • Multiple treatment failures • Personality disorders • Entitlement issues

  8. At Risk Groups for Having Poorly Managed Pain • Children • Elderly people • Minorities and people of color • Substance users/abusers • Women • HIV(+)

  9. Pain in the Elderly . . . Daily pain is prevalent among nursing home residents and is often untreated, particularly among older and minority patients. Bernabei R, et al. JAMA 1998; 279:1877-82

  10. . . . Pain in Elderly 4,003 of 13,625 (38%) patients in 1492 LTCFs experienced daily pain due to Ca • 16% received NSAID or APAP • 32% received combo (CIII) • 26% received morphine (strong opioid) • 26% received nothing at all • Older patients (>85) and minority races were less likely to receive analgesics Bernabei R, et al. JAMA 1998; 279:1877-82

  11. Underestimation of Pain • Providers’ concern about dependence. • Underutilization of analgesics occurs; especially for opioids • Important to differentiate between pain from HIV infection or its complications and pain from therapy; other pain syndromes occur as well Breitbart W et al. Pain 1996; 65: 239. Larue F, Fontaine A & Colleau S. BMJ 1997; 314: 23.

  12. Pain Prevalence in HIV • Estimates of pain prevalence in HIV-infected individuals ranges from 30 to 90% • Prevalence of pain increases as disease progresses • 30% of ambulatory HIV-infected patients in early stages of HIV disease experience clinically significant pain • 56% have had episodic painful syndromes of less clear clinical significance Breitbart W, Passik SD & Rosenfeld BD (1999). Cancer, mind & spirit. Bonica’s Textbook of Pain, 4th Ed., 1065-1112.

  13. All Classes of Medications Are Underutilized in AIDS Pain • < 8% of ambulatory AIDS patients reporting pain in the severe range received a strong opioid • 18% were prescribed nothing whatsoever • 40% were prescribed a non-opioid analgesic • 22% were prescribed a weak opioid analgesic • Only 15% received adequate therapy • Utilizing the Pain Management Index (PMI) • Under medication occurs in only 40% of cancer patients • Adjuvant analgesics were also underutilized • < 10% of AIDS patients reporting pain received adjuvants even though 40% had neuropathic pain Breitbart W, Passik SD & Rosenfeld BD (1999). Cancer, mind & spirit. Bonica’s Textbook of Pain, 4th Ed., 1065-1112.

  14. Headaches • Common complaint from seroconversion to advanced HIV disease • Causes vary widely • Evaluation may require imaging study & lumbar puncture; plus good PE • With CD4 > 200 little need for CT unless focal neurological signs, altered MSE or Sz • Must evaluate all “worst headaches of life” Gifford AL & Hecht FM. Headache 2001; 41: 441. Graham CB et al. Am J Neuroradiol 2000; 21: 451.

  15. Chronic Headaches • Common with HIV • Due to benign, non-infectious cause when early in HIV infection, before onset of significant immunocompromise Masci JR (2001). Outpatient Management of HIV Infections, 3rd Ed., CRC Press, Boca Raton, 118. • Causes are muscle tension, vascular, depression, chronic sinusitis, antiretroviral agents (zidovidine) and chronic opioids Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  16. Meningitis • Most common cause of AIDS-related meningitis is Cryptococcus neoformans • Most infections occur when CD4 < 200 • Meningismus may be absent while headache & fever are common • Other causes of HIV-related meningitis include Strepococcus pneumoniae, Haemophilis influenzae, Neisseria meningitidis, Listeria monocytogenes; HSV/VZV infection; tuberculosis; lymphoma Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  17. Brain Lesions • Headaches with focal neurological abnormalities or seizures; think SOL • Most common: toxoplasmosis • Less common: primary lymphoma, tuberculoma • Many other organisms may cause abscesses of brain with HIV

  18. Other Headache Causes • Sinusitis is more common in HIV-infected than those without HIV • Bacterial, viral and fungal causes • Syphilitic meningitis may occur at any stage of infection with syphilis • JC virus infection causes PML • After LP there may be post-dural puncture headaches from dural leaks Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  19. Oropharyngeal Pain • Candida infections • Gingivitis and periodontitis • Oral ulcers • Neoplasms • Esophageal conditions Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  20. Chest Pain • Fairly common in HIV infection • If pleuritic consider bacterial pneumonia • Think Tb if patient exposed to Tb • Spontaneous pneumothorax associated with Pneumocystitis carinii (PCP) • HAART is associated with insulin resistance & abnormal lipid metabolism • Coronary artery disease may occur Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  21. Back Pain • Most common painful condition reported Singer EJ et al. Pain 1993; 54: 15. • Caused by same musculoskeletal conditions as uninfected people • IVDA may have osteomyelitis of spine with or without epidural abscess • May be due to nephrolithiasis due to indinavir Policar, M & Arumugam, V (in press). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton.

  22. Abdominal Pain • Many etiologies involved, so workup can be challenging and cause “unexplained” potentially • CD4 > 200 are unlikely to have opportunistic causes, but with CD4 < 100 disseminated Myocobacterium avium complex (MAC) must be considered; Cytomegalovirus (CMV) infection of the GI tract occurs when CD4 <50 Policar, M & Arumugam, V (in press). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton. • With HAART incidence of opportunistic infections is decreasing (69 to 13% between 1995 and 1998) Monkemuller KE et al. Am J Gasteroenterol 2000; 95: 457.

  23. Pre-HAART Nonsurgical Causes of Abd Pain • CMV gastritis/enteritis/colitis 20% • Cryptosporidium enteritis 6% • MAC enteritis 9% • Non-Hodgkin’s lymphoma 17% • Pancreatitis 12% • Sclerosing cholangitis 8% • Kaposi’s sarcoma 5% Parente F et al. Scand J Gasterol 1994; 29:511-5.

  24. Causes for Abdominal Pain • HIV-related • Iatrogenic (medication- or procedure-related) • Immune surveillance-related (malignancies) • Non-HIV-related • Nonspecific (resolution without specific diagnosis) Slaven EM et al. Emerg Med Clin North Am 2003; 21: 987.

  25. Non-HIV-RelatedSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987. • Appendicitis • Peptic Ulcer Disease • Diverticulitis • Cholecystitis • Hepatitis • Alcohol-related • Ischemic bowel • Abdominal aortic aneurysm

  26. Immunodeficiency-relatedSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987. • Opportunistic GI infections with MAC, CMV microsporidia • Cholecystitis (CMV) • Abscesses • Sexually transmitted disease-related • Proctitis

  27. Immunosurveillance-relatedSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987. • Lymphomas (GI) • Kaposi’s sarcoma (KS) • Cancer-related obstructions • Other cancers/metastatic disease

  28. Medication-related/iatrogenicSlaven EM et al. Emerg Med Clin North Am 2003; 21: 987. • Perforations secondary to procedures (upper/lower GI tract) • GI upset/reflux/gastritis • Kidney stones (indinavir) • Pancreatitis

  29. Enterocolitis • Most common GI manifestation of HIV • May be acute or chronic, associated with fever and weight loss • Bacteria, viruses, mycobacteria, parasites and fungi are causes • Antimicrobial therapy is indicated; often with antimotility agents for diarrhea Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  30. Pancreatitis • 35-800 times more likely with HIV • HIV meds didanosine, Kaletra and pentamidine; opportunistic infections with CMV, toxoplasmosis, mycobacteria and cryptosporidium; infiltration by lymphoma or KS are causes • Elimination of offending agent (medication, organism) needed Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  31. Appendicitis • Rates of HIV infected similar to non-infected • Usual causes are frequent in HIV, but opportunistic infections may play role • AIDS related pathology found in 30% of cases Whitney TM et al. Am J Surg 1992; 164: 467. • Commonly identified infections associated with appendicitis in HIV are Mycobacterium tuberculosis, MAC and CMV Slaven EM et al. Emerg Clin North Am 2003; 21: 987. • KS seen in cases of AIDS appendicitis Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  32. Cholecystitis • May occur with or without stones • Acalculous twice as common as cholelithiasis • Acalculous associated with infection with Cryptosporidium paarvum, Microsporidium and CMV, plus other pathogens. • Antimicrobials are warranted for infection; surgery may be necessary in general Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  33. Cholangitis • Usually associated with opportunistic infections, malignancy or immunologic destruction of the biliary epithelium • Cryptosporidium and CMV are most common infections • Presents like cholecystitis with CD4 < 100 • Stents can relieve obstruction from strictures; sphincterotomy may help treat pain along with celiac plexus neurolysis Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  34. Intestinal Perforation • Intestinal perforation in HIV infection is uncommon, but commonly caused by CMV related ulceration • Lymphoma, KS, histoplasmosis, peptic ulcer disease and appendicitis too • Treatment is surgery, with antimicrobials or chemotherapy Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  35. Other Abdominal Pain Conditions • Enlarged intra-abdominal lymph nodes • MAC, KS or TB • Intestinal obstruction • KS or lymphoma • Intussesception • Lymphoma, KS or Mycobacterial infection • Toxic megacolon • Tuberculous peritonitis • Abdominal aortic aneurysms Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  36. Rheumatologic and Musculoskeletal Pain • Arthritis and arthropathies • Avascular necrosis • Polymyositis (most frequently seen) • Zidovidine myopathy Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  37. Skin • Various skin conditions cause pain • KS • Decubitus ulcers • Herpes simplex virus (HSV) Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  38. Peripheral Neuropathy • Symptomatic neuropathies occur in 15-50% of patients with HIV; prevalence increases in advanced illness with higher HIV viral load, lower CD4 counts and older age Martin C et al. Eur J Pain 2003; 7: 23. Simpson DM et al. AIDS 2002; 16: 407. Lopez L et al. Eur J Neurol 2004; 11: 97.

  39. Neuropathies Associated with HIV Infection • Distal symmetrical polyneuropathy (DSP) • Antiretroviral toxic neuropathies (ATN) • Herpes zoster (HZ) and post-herpetic neuralgia (PHN) • Mononeuropathy multiplex (MM) • Diffuse infiltrative lymphocytosis syndrome (DILS) • Lumbrosacral polyradiculopathy (cauda equina syndrome) • Mononeuropathies • Inflammatory demyelinating polyneuropathies • Autonomic neuropathy Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  40. Distal Symmetrical Polyneuropathy (DSP) • One of most common HIV neuropathies; presents in middle and late stages • Starts with tingling & numbness in toes, spreads proximally from lower extremities • Painful dysesthesias or numbness occur • DTRs may be decreased or absent • Muscle weakness is not prominent Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  41. Antiretroviral Toxic Neuropathies (ATN) • Occurs at any stage of HIV infection • Indistinguishable from DSP, except for temporal association with initiation of antiretroviral medication • More likely than DSP to be painful, have abrupt onset and progress rapidly • Nucleoside reverse transcriptase inhibitors (NRTIs) are the class most associated with it • “d” drugs: ddl, ddC, d4t • Mitochondrial toxicity may be mechanism Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  42. Herpes Zoster and PHN • HZ, “shingles” results from VZV reactivation • Occurs with age & immunocompromised status • Acute HZ lasts days, healing for weeks; PHN persists > 30 days • PHN pain persists for months to years Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  43. Mononeuropathy Multiplex • MM occurs early or late in HIV infection • In early stages MM is immune mediated; in advanced AIDS can be caused by infection with CMV, Hepatitis B or C, particularly when associated with cryoglobulinemia • Patients present with numbness, tingling, abnormal sensation, burning pain, dysesthesia or paralysis Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  44. Diffuse Infiltrative Lymphocytosis Syndrome • DILS characterized by persistent peripheral blood polyclonal CD8+ lymphocyte expansion • See lymphocytic infiltration of parotid glands, lungs, lymph nodes, lacrimal glands, kidneys, muscles and nerves • Most common is salivary gland enlargement • Peripheral sensory neuropathy with profound muscle weakness is seen Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  45. Lumbosacral polyradiculopathy • Usually associated with CMV infection; also seen with HSV infection, tuberculosis, syphilis or cryptococcal infection • Rapidly progressing cauda equina syndrome can occur with AIDS • Presents with severe back and leg pain associated with LE weakness • Numbness and tingling can begin in feet or saddle region; progression occurs rapidly • Results in flaccid paralysis with incontinence Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  46. Mononeuropathies • Cranial neuropathies • Median at wrist • Ulnar at elbow • Peroneal at fibular head • Phrenic at diaphragm • Present with decreased sensation, tingling, burning pain, weakness and paralysis; impairment of taste and hyperacusis Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  47. Inflammatory Demyelinating Polyradiculoneuropathy • Two major patterns: • Acute inflammatory demyelinating polyneuropathy (AIDP) aka Guillain Barre syndrome (GBS) • Occurs at time of seroconversion (CD4 > 500); evolves rapidly over days to weeks • Chronic inflammatory demyelinating polyneuropathy (CIDP) • Occurs in advanced stages of illness; evolves over weeks • Motor deficit predominates over mild sensory symptoms Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  48. Autonomic Neuropathy • Common in HIV infection • 76-84% having some abnormality • Severity of autonomic dysfunction correlates with progression of HIV disease • Common symptoms include nausea, vomiting, orthostatic hypotension, heat intolerance, diarrhea, constipation, urinary incontinence, bladder dysfunction, impotence, anhidrosis or hyperhydrosis Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

  49. Diagnosing DSP & ATN • Labs unrevealing, but must exclude other causes of this neuropathy so order • B12 and folate levels, TSH, FBS, LFTs, BUN and Cr, Serum protein electrophoresis, immunoelectrophoresis, RPR or VDRL • CSF is acellular with slightly higher protein • EMG & NVC show axonal sensory-motor polyneuropathy • Nerve biopsy shows axonal degeneration of long axons in distal regions; density of unmyelinated fibers is reduced

  50. Diagnosing HZ & PHN • Distinctive rash • Direct immunofluorescent assay • Viral culture Policar, M & Arumugam, V (2006). HIV and AIDS Pain, Weiner’s Pain Management: A Practical Guide for Clinicians, 7th Ed., CRC Press, Boca Raton, 529-542.

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