HIV-related Neuropathy: Difference between revisions
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== Introduction == | == Introduction == | ||
Despite the introduction of combination [[Antiretrovirals and HIV|antiretroviral therapy]] (ART), neuropathies (especially distal sensory neuropathy) are still a common complication of [[Human Immunodeficiency Virus (HIV)|HIV.]] It is associated with significant morbidity.<ref name=":1">Schütz SG, Robinson-Papp J. H[https://www.tandfonline.com/doi/full/10.2147/HIV.S36674 IV-related neuropathy: current perspectives.] HIV/AIDS-Research and Palliative Care. 2013 Sep 11:243-51.</ref> | |||
== Epidemiology == | == Epidemiology == | ||
The prevalence of HIV-associated neuropathy varies from 1.73% tot 69.4% among people living with HIV (PLWH).<ref>Yakasai AM, Maharaj S, Danazumi MS. Strength exercise for balance and gait in HIV-associated distal symmetrical polyneuropathy: A randomised controlled trial. Southern African Journal of HIV Medicine. 2021;22(1).</ref> This | The prevalence of HIV-associated neuropathy varies from 1.73% tot 69.4% among people living with HIV (PLWH).<ref>Yakasai AM, Maharaj S, Danazumi MS. Strength exercise for balance and gait in HIV-associated distal symmetrical polyneuropathy: A randomised controlled trial. Southern African Journal of HIV Medicine. 2021;22(1).</ref> This variability could be attributed to the introduction of ART, with its benefits and varying adverse effects with evolving drug-combinations. Diagnostic criteria and geographical region also influence the he prevalence of HIV-associated neuropathy.<ref name=":0">Howlett WP. [https://www.bioline.org.br/pdf?hs19079 Neurological disorders in HIV in Africa: a review.] African health sciences. 2019 Aug 20;19(2):1953-77.</ref> The estimated pooled frequency of DSN in Africa, prior to ART, was 27%. This increased to 52% in the post-ART era, and was mainly attributed to the widespread use of Nucleoside reverse transcriptase inhibitors (NRTIs) - like Stavudine.<ref name=":0" /> | ||
It is however important to note that although the frequency appears to have increased since the introduction of ART, some studies indicate a significant reduction in pain associated with neuropathy - i.e. although patients test positive for neuropathy (based on signs), it is often asymptomatic.<ref name=":0" /> | It is however important to note that although the frequency appears to have increased since the introduction of ART, some studies indicate a significant reduction in pain associated with neuropathy - i.e. although patients test positive for neuropathy (based on signs), it is often asymptomatic.<ref name=":0" /> | ||
== Clinically Relevant Anatomy | == Clinically Relevant Anatomy == | ||
add text here relating to '''''clinically relevant''''' anatomy of the condition<br> | add text here relating to '''''clinically relevant''''' anatomy of the condition<br> | ||
== | == Pathophysiology == | ||
Although other mechanisms may be at play for the less common types of neuropathy (discussed below), HIV-related neuropathy is usually as a result of '''two distinct pathological processes''' that lead to ''distal axonal degeneration, neuronal loss in the dorsal root ganglia and reduced epidermal nerve fibre density''<ref name=":1" />: | |||
'' | # '''Neurotoxic effect of HIV:''' Indirect neurotoxicity as a result of viral proteins and an inflammatory response to HIV<ref name=":1" /> | ||
# '''Neurotoxic effects of ART:''' Some ART drugs (NRTIs) associated with an increased incidence of peripheral neuropathy. These include Didanosine, Zalcitabine, Stavudine.<ref>Hogan C, Wilkins E. Neurological complications in HIV. Clinical Medicine.2011 Dec;11(6):571.</ref>ART related neuropathy typically develops 5-6 months after initiating ART.<ref name=":0" /> | |||
Despite these two distinct pathological processes, the signs and symptoms of each process are not clinically distinguishable.<ref name=":1" /> | |||
== Clinical Presentation == | == Clinical Presentation == | ||
| Line 28: | Line 30: | ||
Clinical presentation varies depending on the type of neuropathy (discussed below), but may include: | Clinical presentation varies depending on the type of neuropathy (discussed below), but may include: | ||
* Numbness | * Numbness | ||
* Burning pain | * Burning pain | ||
* Altered sensation, including numbness and/or hypersensitivity | * Altered sensation, including numbness and/or hypersensitivity | ||
* Loss of balance as a result of impaired proprioception | * Loss of balance as a result of impaired [[proprioception]] | ||
* Diminished or absent lower limb reflexes | * Diminished or absent lower limb [[reflexes]] | ||
* Muscle weakness and muscle wasting (if motor nerves are affected) | |||
== Diagnostic Procedures == | == Diagnostic Procedures == | ||
Diagnosis is based on medical history and clinical examination. Confirmed HIV infection and NRTI exposure history, along with signs and symptoms related to neuropathy. | |||
Additional tests (mostly to rule out other conditions) may include: | |||
* '''Laboratory tests''' - CD4 count and viral load; Vit B levels; Diabetic screening | |||
* '''[[Nerve Conduction Study|Nerve conduction studies]]''' - not routinely indicated<ref name=":1" /> | |||
* '''[[Quantitative Sensory Testing (QST)|Quantitative Sensory Testing]]''' - will reveal abnormalities in cases of peripheral and central nerve disorders | |||
A clinical diagnostic tool (CHANT) has been validated for use in Africa, and include the following criteria:<ref>Woldeamanuel YW, Kamerman PR, Veliotes DG, Phillips TJ, Asboe D, Boffito M, Rice AS. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072607/ Development, validation, and field-testing of an instrument for clinical assessment of HIV-associated neuropathy and neuropathic pain in resource-restricted and large population study settings.] PLoS One. 2016 Oct 20;11(10):e0164994.</ref> | A clinical diagnostic tool (CHANT) has been validated for use in Africa, and include the following criteria:<ref>Woldeamanuel YW, Kamerman PR, Veliotes DG, Phillips TJ, Asboe D, Boffito M, Rice AS. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072607/ Development, validation, and field-testing of an instrument for clinical assessment of HIV-associated neuropathy and neuropathic pain in resource-restricted and large population study settings.] PLoS One. 2016 Oct 20;11(10):e0164994.</ref> | ||
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* Schwannoma | * Schwannoma | ||
* [[Morton's Neuroma]] | * [[Morton's Neuroma]] | ||
* Thyroid dysfunction | |||
=== B-Vitamins and HIV === | |||
B-vitamin deficiencies are prevalent in PLWH and are associated with poor health outcomes<ref>Layden AJ, Finkelstein JL. [https://www.ncbi.nlm.nih.gov/books/NBK572219/ B-vitamins and HIV/AIDS. Nutrition and HIV: Epidemiological Evidence to Public Health.] 2018 May 15:27-87.</ref> | |||
== Outcome Measures == | == Outcome Measures == | ||
| Line 65: | Line 75: | ||
* HIV-PINS | * HIV-PINS | ||
* BPNS | * BPNS | ||
* [[Quantitative Sensory Testing (QST)|Quantitative Sensory Testing]] | |||
== Types == | == Types == | ||
Neuropathy can occur at all stage of HIV, and various types of neuropathy have been documented. The neuropathies present in PLWH include<ref name=":0" />: | Neuropathy can occur at all stage of HIV, and various types of neuropathy have been documented. The neuropathies present in PLWH include<ref name=":0" />: | ||
# '''Distal sensory neuropathy''' | # '''Distal sensory neuropathy (DSN)''' | ||
# '''Inflammatory neuropathies''' | # '''Inflammatory neuropathies''' | ||
# '''Radiculopathies''' | # '''Radiculopathies''' | ||
| Line 75: | Line 86: | ||
=== 1. Distal Sensory Neuropathy (DSN) === | === 1. Distal Sensory Neuropathy (DSN) === | ||
DSN is the most common type of neuropathy in PLWH.<ref name=":0" />It affects the distal extremities (more commonly the feet) and is caused by axonal damage secondary to dorsal root inflammation. It is more common in the advanced stages of HIV infection (WHO stages 3 and 4). Some patients with DSN (about 25%) do not experiences any sensory symptoms (asymptomatic DSN).<ref name=":0" /> | DSN is the most common type of neuropathy in PLWH.<ref name=":0" />It affects the distal extremities (more commonly the feet, symmetric) and is caused by axonal damage secondary to dorsal root inflammation. It is more common in the advanced stages of HIV infection (WHO stages 3 and 4). Some patients with DSN (about 25%) do not experiences any sensory symptoms (asymptomatic DSN).<ref name=":0" /> | ||
'''Signs and symptoms''' include<ref name=":0" />: | '''Signs and symptoms''' include<ref name=":0" /><ref name=":1" />: | ||
* Burning, stabbing pain and numbness in the soles of the feet/palms of the hands - this ascends symmetrically | * Burning, stabbing pain and numbness in the soles of the feet/palms of the hands - this ascends symmetrically (stocking-glove distribution) | ||
* Sensitivity is most pronounced one the soles and palms | * Sensitivity is most pronounced one the soles and palms | ||
* Reduced or absent ankle reflexes | * Reduced or absent ankle reflexes | ||
* Impaired | * Impaired pin prick and vibration sensation | ||
* Impaired proprioception of the affected region | * Impaired proprioception of the affected region | ||
* Weakness and atrophy are rare as sensory nerves are involved | |||
'''Risk factors''' for developing DSN<ref name=":0" />: | '''Risk factors''' for developing DSN<ref name=":0" /><ref name=":1" />: | ||
* Advanced | * Advanced immunosuppression | ||
* Lower CD4 count and high viral load | * Lower CD4 count and high viral load | ||
* A history of prior TB or alcohol abuse | * A history of prior TB or alcohol abuse | ||
* ART regime that includes Dideoxynucleoside revers transcriptase inhibitors (NRTIs), especially Stavudine | * ART regime that includes Dideoxynucleoside revers transcriptase inhibitors (NRTIs), especially Stavudine | ||
* Height and ethnicity may play a role<ref name=":1" /> | |||
* Diabetes may exacerbate the risk of neuropathy in PLWH<ref name=":1" /> | |||
=== 2. Inflammatory Neuropathies === | === 2. Inflammatory Neuropathies === | ||
Two forms of inflammatory demyelinating polyneuropathy (IDP) can occur in PLWH<ref name=":1" />: | |||
# '''Acute IDP''' [[Guillain-Barre Syndrome|(Guillan-Barré syndrome)]] - rapidly progressive symptoms | |||
# '''Chronic IDP''' - slower progression, often with a relapsing-remitting pattern | |||
Both forms are characterised by ascending muscle weakness and areflexia with paraesthesia<ref name=":1" /> | |||
=== 3. Radiculopathy === | === 3. Radiculopathy === | ||
Radiculopathy in less common and when present usually affects the lumbosacral nerve roots, mostly caused by TB | Radiculopathy in less common and when present usually affects the lumbosacral nerve roots, mostly caused by TB, Cytomegalovirus (CMV) or lymphoma.<ref name=":1" /><ref name=":0" /> | ||
=== 4. Mononeuropathy === | === 4. Mononeuropathy === | ||
The most common mononeuropathies are<ref name=":0" />: | PLWH are at increased risk of mononeuropathies. The most common mononeuropathies are<ref name=":0" />: | ||
* '''Facial nerve palsy (Bell's palsy):''' Usually occurs during the early, asymptomatic stages of HIV (at seroconversion). It may present as part of an acute inflammatory demyelinating neuropathy, but this is less common. | * '''Facial nerve palsy''' ([[Bell's Palsy|Bell's palsy]])''':''' Usually occurs during the early, asymptomatic stages of HIV (at seroconversion). It may present as part of an acute inflammatory demyelinating neuropathy, but this is less common. | ||
* '''Herpes zoster reactivation:''' One of the earliest signs of HIV, and affects the thoracic and trigeminal nerve. Complications include myelitis and post herpetic neuralgia. | * '''Herpes zoster reactivation:''' One of the earliest signs of HIV, and affects the thoracic and trigeminal nerve. Complications include myelitis and post herpetic neuralgia. | ||
* '''Median neuropathy:''' Leading to [[Carpal Tunnel Syndrome|carpal tunnel syndrome]] | |||
== Management | == Medical Management == | ||
* '''HIV infection control -''' early diagnosis and treatment with ART | * '''HIV infection control -''' early diagnosis and treatment with ART | ||
* '''Drug regime alteration if associated with ART -''' Avoiding | * '''Drug regime alteration if associated with ART -''' Avoiding NRTIs; discontinuing Stavudine if symptomatic DSP develops<ref name=":1" /> | ||
* '''Pain control | * '''Pain control''' | ||
** With ''neuropathic medication (''amitriptyline, gabapentin, pregabalin)<ref name=":0" />- Although these medications have proven effectiveness in other neuropathic conditions, they seem to be less effective in HIV-related neuropathy. Gabapentin appears to be superior to other medications.<ref name=":1" /> | |||
** Topical ''capsaicin patches'' have shown promise in reducing neuropathic pain in PLWH<ref name=":1" /> | |||
** Complete resolution of pain is not common, but reduction is possible<ref name=":1" /> | |||
** See the page on [[Neuropathic Pain]] and [[Pain in People Living with HIV|Pain in PLWH]] | |||
* '''Education -''' On possible other causes of neuropathy (alcohol, diabetes and Vit B6 deficiency secondary to isoniazid)<ref name=":0" /> | * '''Education -''' On possible other causes of neuropathy (alcohol, diabetes and Vit B6 deficiency secondary to isoniazid)<ref name=":0" /> | ||
* '''Treatment of other infections -''' in the case of Herpes reactivation, treatment with acyclovir is indicated<ref name=":0" /> | * '''Optimisation of contributing factors''' - medical management of diabetes, alcohol abuse and vitamin deficiencies<ref name=":1" /> | ||
* '''Treatment of other infections -''' in the case of Herpes reactivation, treatment with acyclovir is indicated<ref name=":0" /> | |||
== Role of Physiotherapy == | |||
== Resources == | == Resources == | ||
Revision as of 16:34, 8 December 2023
This article or area is currently under construction and may only be partially complete. Please come back soon to see the finished work! (8/12/2023)
Original Editor - Melissa Coetsee
Top Contributors - Melissa Coetsee, Kim Jackson and Pacifique Dusabeyezu
Top Contributors - Melissa Coetsee, Kim Jackson and Pacifique Dusabeyezu
Introduction[edit | edit source]
Despite the introduction of combination antiretroviral therapy (ART), neuropathies (especially distal sensory neuropathy) are still a common complication of HIV. It is associated with significant morbidity.[1]
Epidemiology[edit | edit source]
The prevalence of HIV-associated neuropathy varies from 1.73% tot 69.4% among people living with HIV (PLWH).[2] This variability could be attributed to the introduction of ART, with its benefits and varying adverse effects with evolving drug-combinations. Diagnostic criteria and geographical region also influence the he prevalence of HIV-associated neuropathy.[3] The estimated pooled frequency of DSN in Africa, prior to ART, was 27%. This increased to 52% in the post-ART era, and was mainly attributed to the widespread use of Nucleoside reverse transcriptase inhibitors (NRTIs) - like Stavudine.[3]
It is however important to note that although the frequency appears to have increased since the introduction of ART, some studies indicate a significant reduction in pain associated with neuropathy - i.e. although patients test positive for neuropathy (based on signs), it is often asymptomatic.[3]
Clinically Relevant Anatomy[edit | edit source]
add text here relating to clinically relevant anatomy of the condition
Pathophysiology[edit | edit source]
Although other mechanisms may be at play for the less common types of neuropathy (discussed below), HIV-related neuropathy is usually as a result of two distinct pathological processes that lead to distal axonal degeneration, neuronal loss in the dorsal root ganglia and reduced epidermal nerve fibre density[1]:
- Neurotoxic effect of HIV: Indirect neurotoxicity as a result of viral proteins and an inflammatory response to HIV[1]
- Neurotoxic effects of ART: Some ART drugs (NRTIs) associated with an increased incidence of peripheral neuropathy. These include Didanosine, Zalcitabine, Stavudine.[4]ART related neuropathy typically develops 5-6 months after initiating ART.[3]
Despite these two distinct pathological processes, the signs and symptoms of each process are not clinically distinguishable.[1]
Clinical Presentation[edit | edit source]
Clinical presentation varies depending on the type of neuropathy (discussed below), but may include:
- Numbness
- Burning pain
- Altered sensation, including numbness and/or hypersensitivity
- Loss of balance as a result of impaired proprioception
- Diminished or absent lower limb reflexes
- Muscle weakness and muscle wasting (if motor nerves are affected)
Diagnostic Procedures[edit | edit source]
Diagnosis is based on medical history and clinical examination. Confirmed HIV infection and NRTI exposure history, along with signs and symptoms related to neuropathy.
Additional tests (mostly to rule out other conditions) may include:
- Laboratory tests - CD4 count and viral load; Vit B levels; Diabetic screening
- Nerve conduction studies - not routinely indicated[1]
- Quantitative Sensory Testing - will reveal abnormalities in cases of peripheral and central nerve disorders
A clinical diagnostic tool (CHANT) has been validated for use in Africa, and include the following criteria:[5]
Differential Diagnosis[edit | edit source]
Also see Neurological Complications of HIV and Neuropathies
- Myelopathy - including Vacuolar Myelopathy and Pott's Disease
- Opportunistic infections affecting the CNS - TB Meningitis, Neurosyphilis, Toxoplasmosis Encephalitis, Cryptococcal Meningitis
- Other CNS conditions - Stroke, Lymphoma, Aseptic Meningitis
- Vitamin B deficiency - Vit B12 deficient or excess of vit B6
- Alcoholic neuropathy
- Diabetic Neuropathy
- Neuropathy related to isolated nerve damage (eg. surgery, compression, traction injury)
- Claudication associated with Peripheral Vascular Disease
- Pain and weakness caused by Central Sensitisation
- Schwannoma
- Morton's Neuroma
- Thyroid dysfunction
B-Vitamins and HIV[edit | edit source]
B-vitamin deficiencies are prevalent in PLWH and are associated with poor health outcomes[6]
Outcome Measures[edit | edit source]
- Neuropathic pain measures: DN4; LANSS; PainDETECT
- Pain intensity: VAS
- The Sensory Peripheral Neuropathy Screen (SPNS)[7]
- HIV-PINS
- BPNS
- Quantitative Sensory Testing
Types[edit | edit source]
Neuropathy can occur at all stage of HIV, and various types of neuropathy have been documented. The neuropathies present in PLWH include[3]:
- Distal sensory neuropathy (DSN)
- Inflammatory neuropathies
- Radiculopathies
- Mononeuropathies
1. Distal Sensory Neuropathy (DSN)[edit | edit source]
DSN is the most common type of neuropathy in PLWH.[3]It affects the distal extremities (more commonly the feet, symmetric) and is caused by axonal damage secondary to dorsal root inflammation. It is more common in the advanced stages of HIV infection (WHO stages 3 and 4). Some patients with DSN (about 25%) do not experiences any sensory symptoms (asymptomatic DSN).[3]
Signs and symptoms include[3][1]:
- Burning, stabbing pain and numbness in the soles of the feet/palms of the hands - this ascends symmetrically (stocking-glove distribution)
- Sensitivity is most pronounced one the soles and palms
- Reduced or absent ankle reflexes
- Impaired pin prick and vibration sensation
- Impaired proprioception of the affected region
- Weakness and atrophy are rare as sensory nerves are involved
Risk factors for developing DSN[3][1]:
- Advanced immunosuppression
- Lower CD4 count and high viral load
- A history of prior TB or alcohol abuse
- ART regime that includes Dideoxynucleoside revers transcriptase inhibitors (NRTIs), especially Stavudine
- Height and ethnicity may play a role[1]
- Diabetes may exacerbate the risk of neuropathy in PLWH[1]
2. Inflammatory Neuropathies[edit | edit source]
Two forms of inflammatory demyelinating polyneuropathy (IDP) can occur in PLWH[1]:
- Acute IDP (Guillan-Barré syndrome) - rapidly progressive symptoms
- Chronic IDP - slower progression, often with a relapsing-remitting pattern
Both forms are characterised by ascending muscle weakness and areflexia with paraesthesia[1]
3. Radiculopathy[edit | edit source]
Radiculopathy in less common and when present usually affects the lumbosacral nerve roots, mostly caused by TB, Cytomegalovirus (CMV) or lymphoma.[1][3]
4. Mononeuropathy[edit | edit source]
PLWH are at increased risk of mononeuropathies. The most common mononeuropathies are[3]:
- Facial nerve palsy (Bell's palsy): Usually occurs during the early, asymptomatic stages of HIV (at seroconversion). It may present as part of an acute inflammatory demyelinating neuropathy, but this is less common.
- Herpes zoster reactivation: One of the earliest signs of HIV, and affects the thoracic and trigeminal nerve. Complications include myelitis and post herpetic neuralgia.
- Median neuropathy: Leading to carpal tunnel syndrome
Medical Management[edit | edit source]
- HIV infection control - early diagnosis and treatment with ART
- Drug regime alteration if associated with ART - Avoiding NRTIs; discontinuing Stavudine if symptomatic DSP develops[1]
- Pain control
- With neuropathic medication (amitriptyline, gabapentin, pregabalin)[3]- Although these medications have proven effectiveness in other neuropathic conditions, they seem to be less effective in HIV-related neuropathy. Gabapentin appears to be superior to other medications.[1]
- Topical capsaicin patches have shown promise in reducing neuropathic pain in PLWH[1]
- Complete resolution of pain is not common, but reduction is possible[1]
- See the page on Neuropathic Pain and Pain in PLWH
- Education - On possible other causes of neuropathy (alcohol, diabetes and Vit B6 deficiency secondary to isoniazid)[3]
- Optimisation of contributing factors - medical management of diabetes, alcohol abuse and vitamin deficiencies[1]
- Treatment of other infections - in the case of Herpes reactivation, treatment with acyclovir is indicated[3]
Role of Physiotherapy[edit | edit source]
Resources[edit | edit source]
add appropriate resources here
References[edit | edit source]
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 Schütz SG, Robinson-Papp J. HIV-related neuropathy: current perspectives. HIV/AIDS-Research and Palliative Care. 2013 Sep 11:243-51.
- ↑ Yakasai AM, Maharaj S, Danazumi MS. Strength exercise for balance and gait in HIV-associated distal symmetrical polyneuropathy: A randomised controlled trial. Southern African Journal of HIV Medicine. 2021;22(1).
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 Howlett WP. Neurological disorders in HIV in Africa: a review. African health sciences. 2019 Aug 20;19(2):1953-77.
- ↑ Hogan C, Wilkins E. Neurological complications in HIV. Clinical Medicine.2011 Dec;11(6):571.
- ↑ Woldeamanuel YW, Kamerman PR, Veliotes DG, Phillips TJ, Asboe D, Boffito M, Rice AS. Development, validation, and field-testing of an instrument for clinical assessment of HIV-associated neuropathy and neuropathic pain in resource-restricted and large population study settings. PLoS One. 2016 Oct 20;11(10):e0164994.
- ↑ Layden AJ, Finkelstein JL. B-vitamins and HIV/AIDS. Nutrition and HIV: Epidemiological Evidence to Public Health. 2018 May 15:27-87.
- ↑ Venkataramana AB, Skolasky RL, Creighton JA, McArthur JC. Diagnostic utility of the subjective peripheral neuropathy screen in HIV-infected persons with peripheral sensory polyneuropathy. The AIDS Reader. 2005 Jul 1;15(7):341-4.
