|
Tools for Grantees: |
A
Guide To Primary Care For
People With HIV/AIDS, 2004 edition |
<
Previous
| Home | Next >
Chapter
8
Symptom Management
Tara Evans
Nysoe, MD
Douglas S. Paauw, MD, FACP
Workup
of Symptoms
TOP
How should
you approach the workup of symptoms in patients infected with HIV?
Symptom evaluation
in HIV-infected patients must include knowledge of the CD4 count
and viral load as well as close attention to the medication list.
An opportunistic disease (OD) is an unlikely cause of symptoms in
patients with CD4 cell counts >200/mm3. Antiretroviral medications
are a common cause of HIV-related symptoms.
Medication-Related
Issues
TOP
What are
the most common symptoms related to antiretroviral medications?
Nausea and
diarrhea are the two most common symptoms associated with antiretroviral
therapy (ART). Pruritus and skin rashes are also common, especially
with nonnucleoside drugs. Lower extremity pain due to neuropathy
is seen with didanosine (ddI), stavudine (d4T), and zalcitabine
(ddC).
What are
the common side effects of each of the antiretroviral drugs?
The different
classes of drugs have many similar as well as distinct side effects
(see Table 8-1).
Table
8-1. Side Effects of
Antiretroviral Drugs
Nucleosides
(NRTIs)
|
Class
effect |
Hepatic
steatosis/lactic acidosis |
abacavir
(ABC) |
Hypersensitivity
reaction (nausea, anorexia, fever, rash, dyspnea, cough) |
didanosine
(ddI) |
Pancreatitis,
peripheral neuropathy, nausea, diarrhea |
lamivudine
(3TC) |
Very
few side effects |
stavudine
(d4T) |
Peripheral
neuropathy, pancreatitis |
tenofovir
(TDF) (a nucleotide) |
Nausea,
vomiting, diarrhea |
zalcitabine
(ddC) |
Peripheral
neuropathy, mucosal ulcers, pancreatitis |
zidovudine
(AZT) |
Anemia,
myopathy, headache, nausea |
emtricitabine
(FTC) |
Nausea,
very few side effects |
Non-nucleoside
Reverse Transcriptase Inhibitors (NNRTIs)
|
efavirenz
(EFV) |
Confusion,
insomnia, rash, disturbing dreams |
nevirapine
(NVP) |
Rash
(15%), hepatitis |
Protease
Inhibitors (PIs)
|
Class
effect |
Hyperglycemia,
hyperlipidemia, lipodystrophy, hepatitis |
amprenavir
(APV) |
Nausea,
diarrhea, rash, paraesthesias |
atazanavir
(ATV) |
Elevated
bilirubin |
fosamprenavir
(FAPV) |
Diarrhea |
indinavir
(IDV) |
Nausea,
renal sludging, renal stones, increased indirect bilirubin |
lopinavir+ritonavir
(LPV/r or Kaletra) |
Nausea,
vomiting, diarrhea |
nelfinavir
(NFV) |
Diarrhea
common (can be limiting) |
ritonavir
(RTV) |
Nausea,
vomiting, circumoral paraesthesias, hepatitis, taste abnormalities |
saquinavir
(SQV) |
Nausea,
diarrhea |
What symptoms
could be due to life-threatening acute drug reactions?
Symptoms of
life-threatening acute drug reactions are not to be missed. A patient
with myalgias, nausea, vomiting, diarrhea, abdominal pain, fever,
rash, malaise, and extreme fatigue who has started taking abacavir
(ABC) within the previous 6 weeks is probably suffering from an
abacavir hypersensitivity reaction. In this case, abacavir should
be permanently discontinued. The hypersensitivity reaction occurs
in up to 5% of patients starting on abacavir and can lead to hypotension
and death if the patient is rechallenged with abacavir. If a patient
taking one of the "d-drugs" (didanosine [ddI], zalcitabine
[ddC], stavudine [d4T], dapsone [for Pneumocystis pneumonia prophylaxis])
has rapid onset of nausea/vomiting and constant, severe abdominal
pain in the epigastrium or upper quadrants that radiates to the
back, drug-induced pancreatitis is possible. Patients taking a nucleoside
(NRTI) who have vague symptoms including nausea, vomiting, abdominal
pain, weight loss, malaise, fatigue, dyspnea, or fever must have
lactic acidosis with hepatic
steatosis ruled out. This occurs 5-13 months after initiating therapy
and has a 60% fatality rate. Patients taking
nevirapine (NVP) who have fatigue, malaise, nausea, vomiting, jaundice,
and right-upper-quadrant abdominal pain could have nevirapine-induced
hepatitis. Also, up to half the patients taking nevirapine may have
a rash; however, if the rash is moist, involves the mucous membranes,
or is extensive with an associated fever, Stevens-Johnson syndrome,
which also occurs in patients taking trimethoprim-sulfamethoxazole
(TMP/sulfa), must be considered. Severe cases of Stevens-Johnson
syndrome, including toxic epidermal necrolysis (TEN), are medical
emergencies and must be managed as burn cases. For all drug-induced,
life-threatening illnesses, immediate discontinuation of the offending
drug is the crucial first step in care.
What are
the most important drug interactions that occur with antiretroviral
medications?
Drug interactions
are frequently the cause of symptoms and must be closely watched
for. Not only do antiretroviral drugs react with each other, they
react with numerous prescribed drugs and recreational drugs (see
Tables 4-8 in the Pocket Guide).
What natural
products are potentially useful in treating the symptoms of patients
with HIV?
Some commonly
used complementary medicine treatments are listed in Table 8-2.
Ginger for the treatment of nausea is probably the most effective
of the natural products for symptom management.
Table
8-2. Complementary Medicine Treatment Options
for Various Symptoms
Nausea |
Ginger |
Studies
have shown possible benefit. |
Hepatitis |
Milk
thistle |
Inconclusive
long-term benefit; may inhibit the p450 system. |
Migraine
prophylaxis |
Riboflavin |
Randomized
controlled trial showed benefit. |
Immune
system dysfunction |
Co-enzyme
Q |
Studies
have shown possible benefit in CD4 cell counts but no outcome
benefit has been shown |
Nausea
TOP
What are
the important causes of nausea in patients with HIV?
The most common
cause of nausea in patients with HIV is medication side effects.
Many of the antiretroviral drugs can result in prominent nausea.
Full dose ritonavir (RTV) probably causes the most severe and frequent
symptoms, but nausea can be seen with all of the protease inhibitors
(PIs). Zidovudine (AZT) frequently causes nausea when first taken.
Didanosine (ddI), stavudine (d4T), and zalcitabine (ddC) can all
cause nausea, or nausea may be an early sign of the pancreatitis
these drugs can lead to. All classes of antiretroviral drugs can
cause hepatitis, which may present as intense nausea and fatigue.
Nevirapine (NVP) and PIs are the most likely to do this, but nucleosides
can cause life-threatening lactic acidosis in association with hepatic
steatosis. Nausea can be a component of abacavir (ABC) hypersensitivity
reaction, usually associated with fever, rash, vomiting, and anorexia.
The commonly used antibiotics trimethoprim-sulfamethoxazole
(for Pneumocystis pneumonia [PCP] prophylaxis) and azithromycin
or clarithromycin (for Mycobacterium avium complex [MAC] prophylaxis)
can cause nausea.
Nonmedication
causes to consider include viral hepatitis (acute hepatitis A, B,
or C). Nausea is a common feature of cryptococcal meningitis; other
sources of increased intracranial pressure such as CNS lymphoma
or toxoplasmosis can also present with severe nausea and vomiting.
What are
the best options for managing nausea?
If nausea is
due to medications, stopping the medication or removing an interacting
drug is the best option. Symptomatic therapy with prochlorperazine
or metoclopramide may help. A natural product option is ginger,
at a dose of 2 grams daily (no more than 4 grams/day). Switching
the time of the dose of the offending drug to be taken with food
may be helpful.
Pulmonary
Symptoms
TOP
What are
the possible causes of cough in an HIV-infected patient?
The CD4 cell
count is crucial information in determining the cause of cough.
In patients with CD4 cell counts >200/mm3, viral upper respiratory
infections, bacterial pneumonia (caused by S. pneumoniae or H. influenzae
most commonly), tuberculosis (TB), and sinusitis with post-nasal
drip are all important causes of cough. Bacterial bronchitis is
more common in patients with HIV than in non-HIV-infected patients.
In patients with low CD4 cell counts (<200/mm3) Pneumocystis
carinii pneumonia must be considered. The risk of PCP is markedly
diminished if the patient is taking trimethoprim-sulfamethoxazole
for PCP prophylaxis. The cough that occurs with PCP is usually dry
and persistent and will usually have been present for several weeks
before a patient seeks evaluation. Fungal disease due to cryptococcus,
histoplasmosis, or coccidioidomycosis is more common with lower
CD4 cell counts.
What workup
is appropriate?
In patients
with CD4 cell counts >200/mm3 the history and physical exam should
determine what testing to do. If the patient has a cough but no
fever or productive sputum, no dyspnea, and a normal pulmonary exam,
then chest x-ray is not necessary. A patient at high risk for TB
should have an x-ray if there is a prolonged cough (>2-3 weeks)
regardless of CD4 cell count. In a patient with a low CD4 cell count
(<200/mm3) the possibility of PCP is much more likely and an
aggressive approach is warranted; a chest x-ray can begin the workup.
If it is normal, then consider obtaining oxygen saturation measurements
with ambulation. An individual who has oxygen desaturations should
have further workup. For evaluation of suspected PCP see Chapter
9, Management of Opportunistic Diseases.
Are patients
infected with HIV at increased risk of developing bacterial pneumonia?
Available data
clearly suggest that HIV-infected patients have an increased risk
of developing bacterial pneumonia. In the 1993 CDC classification
system, recurrent pneumonia (2 or more episodes in 1 year) is defined
as a category C (AIDS-indicator) condition. Pneumococcal pneumonia
is the most common bacterial pneumonia in persons infected with
HIV, and it occurs approximately 10 times more frequently than in
persons not infected with HIV. In addition, the development of pneumococcal
pneumonia can occur early in the course of HIV disease, before other
manifestations of immune suppression. HIV-infected persons with
pneumococcal pneumonia have clinical signs and symptoms similar
to those in HIV-negative individuals, but they have an approximately
20-fold higher risk of developing pneumococcal bacteremia. Treatment
of pneumococcal pneumonia is generally the same in persons with
and without HIV infection. Several studies have shown that HIV-infected
persons have a slightly increased risk of developing pneumonia caused
by Pseudomonas aeruginosa.
How common
is sinus disease in patients with HIV?
Sinus disease
is very common in patients with HIV. The lower the CD4 cell count,
the more severe and more widespread (number of sinuses involved)
sinusitis is. In patients with lower CD4 cell counts, chronic sinusitis
and lack of response to therapy are more common. The most common
organisms involved are Streptococcus pneumoniae, Streptococcus viridans,
and Pseudomonas aeruginosa. Pseudomonal sinus infections are more
common in patients with CD4 cell counts of <50/mm3. Fungal (Aspergillus)
and viral (Cytomegalovirus) sinusitis can occur in patients with
CD4 cell counts <100/mm3. Aggressive treatment of sinus disease
with saline irrigation, antihistamine/decongestant combinations
and full-dose nasal steroids is appropriate. Antibiotics should
be given for the normal duration for episodes of acute sinusitis
(3-6 week course). If antibiotic therapy and aggressive irrigation
do not resolve the problem, referral to an ENT specialist for drainage
procedures and for consideration of sinus surgery is appropriate.
Fatigue
TOP
What are
the common causes of chronic fatigue in patients with HIV?
Fatigue can
have a large impact on the quality of a patient's life. Common descriptors
of fatigue include tiredness, weakness, lack of energy, sleepiness,
and exhaustion. Of the many possible causes of chronic fatigue in
patients with HIV, the most common is depression. Other psychosocial
causes include stress, anxiety, use of recreational substances,
sleep disturbances, domestic abuse, and lack of exercise. ODs must
be considered as a possible cause of fatigue in patients with low
CD4 cell counts. Other disease states such as anemia, hypothyroidism,
hypogonadism, adrenal insufficiency, influenza and other non-opportunistic
infections, diabetes, liver disease, and malnutrition can also present
as fatigue. Fatigue can be a side effect of ART and other medications
commonly taken by patients with HIV. HIV-associated fatigue is a
diagnosis of exclusion.
How do you
determine the cause of a patient's fatigue?
Ask if the
patient is having other symptoms of depression: change in sleep
or appetite patterns, depressed mood, anhedonia, agitation or retardation,
difficulties with concentration, decreased self-esteem, and suicidal
ideation. Take a thorough social history and determine if multiple
life stressors are present. Inquire as to how many hours of sleep
the patient is getting per night and the number of middle-of-the-night
awakenings; ask if the patient feels rested in the morning. Important
history questions that help differentiate a physical from a psychological
etiology for fatigue are in Table 8-3. Identify any barriers to
effective sleep. Ask about the patient's diet and exercise habits,
and determine if the patient drinks alcohol or uses recreational
drugs, including caffeine. Thoroughly review the patient's medication
list and identify any medications, such as certain antiretroviral
drugs, beta-blockers, antihistamines, etc., that can be associated
with fatigue. Do a complete review of systems and physical exam
to elicit other symptoms or signs that may suggest an OD or other
disease state. Simple laboratory tests, such as alanine aminotransferase
(ALT), blood glucose, thyroid stimulating hormone (TSH), and hematocrit,
can help to rule out common diseases that can cause fatigue. Electrolyte
abnormalities can suggest adrenal insufficiency. Order other laboratory
or diagnostic tests as symptoms and signs direct.
Table
8-3. History Questions to Differentiate Physical from
Psychological Causes of Fatigue
Question |
Pshychological
Cause |
Physical
Cause |
Onset |
Often
follows problem or conflict. |
Related
to onset of physical ailments. |
Duration |
Chronic |
Of
recent onset. |
Progression |
Fluctuates |
Increases
as disease advances. |
Effect
of Sleep |
Unaffected
by sleep. |
Relieved
by sleep. |
Diurnal |
Present
in morning, may improve. |
Increases
as the day progresses. |
Neuropathic
Pain
TOP
What is
the most common cause of neuropathic pain and paresthesias in patients
with HIV?
Distal symmetrical
polyneuropathy (DSP) is most commonly caused by antiretroviral drugs.
The drugs didanosine (ddI), zalcitabine (ddC), stavudine (d4T) can
all cause DSP at high doses. Studies have shown zalcitabine to be
the most likely to cause neuropathy at standard doses; concurrent
alcohol use or vitamin B12 deficiency may increase risk. HIV-related
DSP is less common than drug-induced DSP. The two types of neuropathies
present similarly, although onset may be more acute in drug-induced
DSP. HIV-related DSP does not appear to respond to viral suppression
with ART.
How do you
diagnose and treat DSP?
Diagnose drug-related
DSP by linking the onset of the symptoms with the initiation of
drug therapy. Treat by drug removal; symptoms may worsen temporarily
but should regress within several weeks. Residual painful symptoms
of DSP may be treated with tricyclic antidepressants, narcotic analgesics,
or gabapentin. The topical medication capsacin may be helpful if
the neuropathy is limited to a small surface area.
Dermatologic
Symptoms
TOP
How do you
manage generalized pruritus in a patient with no cutaneous signs
on exam?
If a patient
with HIV has generalized pruritus with no obvious cutaneous diagnosis,
acute drug reactions such as Stevens-Johnson syndrome, which can
be life-threatening, and coexisting systemic illness such as hepatic
dysfunction must be ruled out (see Table 8-4 and earlier section
on medication-related issues). Order a complete blood count, liver
function tests, and blood chemistries. Occasionally, scabies can
present with minimal to no cutaneous signs. Pruritus due solely
to HIV infection is a diagnosis of exclusion; it can respond to
ART. (Symptomatic treatments for generalized pruritus are listed
in Table 8-5.) In general, if a clear cause is not identified, xerosis,
a common condition in patients with HIV disease, will be the most
likely diagnosis. In this case, decreasing the amount of bathing,
avoiding dry soaps, using emollient creams, and ceasing scratching
are the basis of symptomatic treatment. In addition, general agents
such as H-1 antagonists can be used. The best studied of these is
hydroxyzine, which offers the benefit of sedation for nocturnal
itching.
Table
8-4. Common Causes of Pruritus in Patients with HIV
Very
common
- Staphylococcal
folliculitis
- Xerosis
- Atopic
dermatitis
- Scabies
- Psoriasis
- Hypersensitivity
to insect bites
- Drug
reactions
Less
common
- HIV-associated
pruritus
- Eosinophilic
folliculitis
- Granuloma
annulare
- Lymphoma
- Hepatic
failure
- Renal
failure
|
How does
scabies manifest differently in HIV-infected persons?
Among HIV-infected
persons with mild-to-moderate immune suppression, scabies causes
similar clinical manifestations as seen in persons without HIV infection,
namely multiple pruritic papular lesions. Treatment consists of
applying 30-60 g of 5% permethrin cream to the entire body from
the neck down, leaving it on for 8-12 hours, then washing it off,
and repeating the entire process one week later. In HIV-infected
persons with severe immune suppression (CD4 count of <100 cells/mm3),
an atypical form of scabies known as crusted or "Norwegian"
scabies may develop. Crusted scabies is characterized by an enormous
number of scabies mites and manifests as nonpruritic, thick, grayish-white,
plaque-like lesions. In severe cases, the large lesions can develop
deep fissures. Treatment of crusted scabies consists of ivermectin
200µg/kg orally with a repeat dose a week later.
Table
8-5. Therapy Strategies and Treatment Options
for Generalized Pruritus
Prevention
of scratching |
Scratching
causes secondary irritation |
Lubrication
with ointments and creams with a fatty basis |
e.g.,
propylene glycol, wax esters |
Avoidance
of histamine induction by heat |
e.g.,
bathing in lukewarm or cold water |
Avoidance
of irritating substances |
e.g.,
alkaline soaps, wool clothing |
Antihistamines |
The
evidence is sparse; watch for side effects |
Topical
agents
- Coolants
- Anesthetic
agents
|
e.g.,
menthol, phenol
e.g., EMLA® Cream (lidocaine 2.5% and prilocaine 2.5%)
|
Lindane |
Empiric
treatment for scabies if risk factors |
UVB
therapy |
Three
times a week, up to 20 treatments for maximal benefit |
Hypnosis |
Studies
have demonstrated benefit |
What are
the causes and treatments of blisters and cutaneous ulcers in persons
with HIV?
Several studies
have suggested that HIV-infected persons, when compared with age-matched
HIV-negative persons, have an approximately 10-fold increased risk
of developing "shingles," a complication resulting from
reactivation of varicella-zoster virus. Herpes zoster can occur
at any CD4 cell count and thus does not require advanced HIV-related
immune suppression. Indeed, the development of herpes zoster may
serve as one of the first clinical events prompting an HIV-infected
person to seek medical care. Persons with HIV can have more than
one episode of herpes zoster. For unknown reasons, HIV-infected
persons who start aggressive ART have an increased risk of developing
herpes zoster in the 6-month period after starting ART; in this
scenario, the herpes zoster does not reflect worsening immunologic
function or waning effectiveness of ART.
Because immune-suppressed
persons who develop herpes zoster have an increased risk of disseminated
herpes zoster, most experts recommend that all HIV-infected persons
with zoster receive therapy. As long as the patient has no evidence
of disseminated disease, central nervous system disease, or cranial
nerve involvement, oral therapy can be used. Therapy for localized
dermatomal zoster consists of 7-10 days of oral therapy with valacyclovir
(1000 mg tid), acyclovir (800 mg 5x/day), or famciclovir (500 mg
tid). In addition, acute zoster-associated pain often requires therapy.
Therapy for zoster in HIV-infected persons should not include corticosteroids.
No evidence exists to suggest HIV-infected persons have a higher
risk of developing post-herpetic neuralgia as a complication of
zoster infection.
Among HIV-infected
persons with mild or moderate immune suppression (CD4 count >350
cells/mm3), herpes simplex virus (HSV) infections cause clinical
manifestations similar to those in HIV-negative persons, namely
self-limited oral or genital lesions that typically appear with
vesicular or ulcerated lesions. Recommended therapy for episodic
HSV infection consists of either acyclovir 400 mg po tid x 5-10
days, famciclovir 500 mg po bid x 5-10 days, or valacyclovir 1000
mg po bid x 5-10 days. In persons with more advanced immune suppression,
particularly those with severe immune suppression (CD4 count <100
cells/mm3), HSV infection may present as a non-healing, large, ulcerated
lesion anywhere on the body. Therapy for these chronic, ulcerated
lesions typically requires longer duration. In addition, those HIV-infected
persons with severe immune suppression who receive chronic suppressive
therapy for HSV have an increased risk of developing acyclovir-resistant
HSV infection.
How does
molluscum contagiosum manifest in severely immunosuppressed persons
with HIV?
Among HIV-infected
patients with severe immune suppression (CD4 count <100 cells/mm3),
molluscum contagiosum typically presents as flesh-colored, papular
lesions, most often on the face, neck, chest, or genitalia. In contrast
to immune competent patients who typically have a self-resolving
illness, HIV-infected persons with severe immune suppression generally
have a progressive increase in the number and size of the molluscum
lesions, often culminating in very large and disfiguring lesions
referred to as "giant molluscum." These lesions are particularly
problematic if located on the face. Extremely large lesions may
require surgical removal, moderate-sized lesions typically respond
to liquid nitrogen therapy, and multiple small lesions are best
treated with topical tretinoin 0.025% applied once a day. In addition,
effective ART with improvement in immune function may help in managing
molluscum.
How do you
recognize and treat seborrheic dermatitis?
Although seborrheic
dermatitis is a well-known dermatologic disorder in persons who
do not have HIV infection, this disorder occurs with increased frequency
and severity among HIV-infected persons. Patients with HIV infection
and seborrheic dermatitis typically have symmetrical erythematous,
scaled patches and flaking, most often on the scalp, eyebrows, beard,
central chest, and axillae. Typically, seborrheic dermatitis spares
the central part of the face. Most patients respond to topical antifungal
creams, such as 2% ketoconazole cream. In some instances, adding
1% hydrocortisone cream may be required.
Mouth
Lesions
TOP
Many patients
with HIV have mouth pain: what are the most common mouth lesions?
The two most
common oral lesions in HIV patients are oral candidiasis and oral
hairy leukoplakia; they are clinical markers of symptomatic HIV
infection. Oral hairy leukoplakia is a raised, white lesion that
is usually seen on the lateral surface of the tongue. Hair-like
projections can occasionally be visualized. It is usually asymptomatic,
but may cause discomfort and impair taste and eating as it grows
in size. The lesion appears more frequently in patients with lower
CD4 counts and is thought to be caused by the Epstein-Barr virus.
Mucosal candida
infections are seen as the CD4 cell count falls below 200-300 cells/mm3.
The manifestations vary; they can involve the hard and soft palates,
buccal mucosa, tongue, pharynx, and hypopharynx. The most common
presentation is pseudomembranous candidiasis, or thrush. "Cottage
cheese" plaques are seen on the soft palate, tonsils, and buccal
mucosa and can be removed with a tongue blade. Atrophic candidiasis
is a less seen and underdiagnosed form of candidiasis, consisting
of flat, erythematous plaques in the same distribution as pseudomembranous
candidiasis but lacking the white exudates. Mouth pain and loss
of acuity of taste are common symptoms with atrophic candidiasis.
Diagnosis of
a candida infection is commonly based on physical exam findings.
Examination of a KOH preparation of a plaque scraping may also be
used; culturing is rarely necessary. Response to a trial of topical
antifungal agents (clotrimazole troches are easier than liquid nystatin
to use) establishes the diagnosis. If the above diagnostics do not
suggest Candida, a biopsy of the lesion may be performed. Oral hairy
leukoplakia needs to be treated only if it causes mouth pain. It
can be treated with high-dose acyclovir, valacyclovir, or famciclovir.
What are
the causes of painful oral ulcers in patients with HIV?
Oral ulcers
are common in patients with HIV. HSV causes primary or recurrent
small, smooth, painful ulcers on the lips, gums, hard palate, or
buccal mucosa. They can present as solitary lesions or in clusters.
Lesions often last weeks, and treatment with acyclovir can shorten
the course. Patients with disseminated cytomegalovirus (CMV) infection
can occasionally have a large, solitary oral lesion. Aphthous stomatitis
can present as single or multiple painful ulcers on the buccal and
labial mucosa and the lateral aspect of the tongue. Aphthous ulcers
are often exudative or necrotic in patients with HIV, and the course
is usually more prolonged than in patients without HIV. Drug therapy
with zalcitabine (ddC) can also cause ulcers. In managing oral ulcers,
biopsy and viral culture establishes the etiology; some suggest
treating empirically for HSV. If the lesion is consistent with aphthous
ulcers, treat either with topical or oral steroids or thalidomide.
An oral suspension consisting of diphenhydramine, viscous lidocaine,
tetracycline, and dexamethasone may offer some pain relief. Removal
of the offending drug is the treatment for drug-induced ulcers.
How do you
recognize and treat gingivitis and periodontal disease?
These diseases
can develop either insidiously or abruptly in patients with HIV
and may be severe. Gingivitis is common and can occur at any CD4
cell count. Severe pain, foul breath, bleeding gums, and loosening
of teeth are common symptoms, and exam may show a bright red marginal
line on the gingiva, gingival erosion, necrosis and ulceration of
interdental papillae, exfoliation of enamel, and loose teeth. The
cause is unclear, although aerobic and anaerobic gram-negative bacteria,
spirochetes, and yeast have been implicated. Severe, ulcerating
gingivitis can be caused by Klebsiella pneumoniae, Enterobacter
cloacae, and other gram-negative bacilli. Treatment includes debridement,
irrigation with povidone-iodine/chlorhexidine oral solutions, and
topical antiseptic agents or metronidazole.
Wasting
TOP
What are
the common causes of weight loss and wasting in patients with HIV?
There can be
many different psychological and physical causes of weight loss
in HIV disease (see Table 8-6).
Table
8-6. Common Causes of Weight Loss
in Patients with HIV
Inadequate
dietary intake resulting from:
- Depression
- Painful
oral lesions
- Esophageal
lesions causing dysphagia
- Reduced
taste sensation (thrush/meds)
- Medication
side effects (eg, nausea)
Chronic
diarrhea (malabsorption) resulting from:
Hypermetabolic
states
Infection
Occult malignancy (eg, B-cell lymphoma)
Endocrine problems:
- Hypogonadism
- Adrenal
insufficiency
- Diabetes
(PI-induced)
|
How do you
work up a patient with weight loss and wasting?
The workup
is driven by results of the history, physical exam, and CD4 cell
count; a higher CD4 count is more suggestive of causes such as endocrine
disorders, malignancies, depression, or medication side effects.
Serum testosterone, glucose, and thyroid tests to assess hormone
status may be ordered. If malnutrition is suspected, it is important
to address this promptly, since malnutrition decreases the function
and number of immunity cells and leads to increased morbidity and
mortality. Evaluation of GI function, calculation of caloric intake,
estimation of protein and energy requirements, measurement of serum
prealbumin, albumin, folate, and vitamin B12, and determination
of the extent of lean body mass lost make up a comprehensive nutritional
assessment. Body cell mass can be measured using mid-arm circumference.
Specific dietary deficiencies should be addressed, vitamin and mineral
supplements should be prescribed, and high-calorie protein-containing
foods should be recommended. In the patient with a low CD4 count
(<100 cells/mm3), OIs such as Mycobacterium avium complex (MAC),
tuberculosis, cytomegalovirus infection, cryptosporidiosis, and
Pneumocystis carinii pneumonia (PCP) should be ruled out, as well
as lymphoma. Order a complete blood count, chemistries, blood cultures,
chest x-ray, oximetry, and gastrointestinal biopsies or stool cultures
as indicated. Referral to a nutritionist or registered dietician
is often helpful. Also see Health Care and HIV: Nutritional Guide
for Providers and Clients under Suggested Resources for practical
assessment tools and algorithms for providers as well as patient
handouts.
What are
the medical treatment options for AIDS wasting?
If an underlying
cause of wasting has been identified, treatment of that cause is
the first step in restoring weight. One important factor may be
switching to ART that does not cause gastrointestinal/anorexia symptoms
preventing food intake. Any infectious process should be identified
and treated. For nonspecific AIDS wasting, the mainstay of treatment
is nutritional supplementation along with appetite stimulants and
antiemetics. Institution of ART and prevention of OIs are important
in restoring weight. Human growth hormone has been shown to rebuild
lean body mass, although it is expensive and survival advantage
is controversial; some recommend that it be reserved for patients
who have intractable, unexplained weight loss and require short-term
treatment to maintain body cell mass during an acute illness (see
Table 8-7 for treatment options).
Table 8-7. Treatment Options for Specific Causes of Weight Loss
Anorexia |
Appetite stimulants
- dronabinol
2.5-5 mg/d
- megestrol acetate 800 mg/d
|
Some studies show that weight gained is from body fat and not lean body stores. Megestrol can raise blood sugar levels, especially when used with protease inhibitors. |
Hypogonadism |
testosterone
- IM 200-300 mg every 2-3 weeks
- Transdermally
- Patch 5 mg/day
- 1% gel 5-10 g/day
oxandrolone
nandrolone
|
Liver function tests must be monitored with use of oral anabolic agents. |
Myalgias
TOP
What are
some common causes of myalgias in patients with HIV?
HIV can cause
an inflammatory myopathy at any stage of infection. Symptoms include
slowly progressive, proximal muscle weakness of the extremities
with or without myalgias. Myopathy due to zidovudine (AZT) toxicity
presents similarly to HIV-associated myopathy, and it may be difficult
to distinguish between these two disorders. Zidovudine toxicity
occurs usually after several months of therapy (most commonly after
6 or more months of continual therapy). Myopathy or rhabdomyolysis
due to HMG coenzyme A reductase inhibitors (statins) or fibrates
are another important concern with HIV-infected patients. Many patients
are on these drugs for treatment of hyperlipidemia caused by treatment
with PIs. PIs decrease the metabolism of statins, which can increase
the chance of toxicity. Moreover, many patients are on both gemfibrozil
and a statin, which can interact to increase the risk of muscle
toxicity. Simple myalgias are more common than rhabdomyolysis or
myopathy caused by the statins.
How do you
evaluate and manage a patient with myalgias or myopathy?
The first step
is to check creatinine phosphokinase (CPK) levels. This should be
done for any patient on zidovudine (AZT) or a statin who has symptoms
of myalgias or muscle weakness. Periodic (every 3-6 months) monitoring
of CPK levels is appropriate for patients who are on a statin/PI
or statin/gemfibrozil combination. Muscle biopsy should be performed
if signs and symptoms of myopathy do not remit within about a month
after drug removal or if a patient has muscle enzyme elevations
and is not on a drug known to cause muscle damage. Organisms may
be seen on muscle biopsy, indicating an infectious myopathy. If
no organisms are seen and there are signs of inflammation on biopsy,
an inflammatory myopathy secondary to HIV is likely, and a trial
of corticosteroids or therapy with intravenous immune globulin (IVIG)
should be implemented.
Diarrhea
TOP
What are
the common causes of diarrhea in patients with HIV?
The main causes
of diarrhea are related to either infections or medications. Infectious
diarrhea can be caused by a number of organisms, dependent on the
patient's CD4 cell count (see Table 8-8). Nelfinavir (NFV) is the
antiretroviral drug most commonly associated with diarrhea. All
the PIs can cause diarrhea. Didanosine (ddI) is the nucleoside most
associated with diarrhea, but diarrhea is less common when the enteric
coated (EC) form is used. Metformin, a drug used for treatment of
lipodystrophy syndrome and diabetes, commonly causes diarrhea.
Table
8-8. Infectious Causes of Diarrhea in Patients with HIV
Any
CD4 cell count (acute diarrhea)
Viruses
(especially Norwalk virus)
Clostridium difficile (previous antibiotic exposure)
Salmonella spp
Shigella spp
Campylobacter spp
Any
CD4 cell count (chronic diarrhea)
Clostridium
difficile
Giardia lamblia
CD4 count <300 cells/mm3 (chronic diarrhea)
Microsporidia
Cryptosporidia
Mycobacterium avium complex (CD4<100)
Isospora belli
Cytomegalovirus (CD4 count <100/mm3)
Idiopathic
|
What is
the best approach to the evaluation of chronic diarrhea in the patient
with HIV?
For patients
who are on medication that can cause intractable diarrhea, one option
is a trial of antidiarrheal medications (loperamide or atropine/phenoxylate
either alone or in combination) and continuation of the previous
antiretroviral regimen. If this does not work, another option is
a trial off medication. If a patient is on ART, stop all medications
for the 1-week evaluation period. If there is a response, then a
new agent can be substituted for the most likely causative drug,
usually nelfinavir (NFV) or lopinavir plus ritonavir (LPV/r, or
Kaletra). If there is no response when medications are stopped,
then stool studies should be done. If the patient has a high CD4
cell count (>300/mm3), start with C. difficile toxin and Giardia
antigen. If the CD4 cell count is low (<300/mm3), do a full workup
with C. difficile, Giardia antigen,
Microsporidia/Cryptosporidia
assay, and modified AFB stain for cryptosporidia. If no organisms
are identified, in patients with very low CD4 cell counts (<100/mm3)
obtain blood cultures for Mycobacterium avium, and if these are
negative, pursue lower endoscopy with particular emphasis on detection
of cytomegalovirus on biopsy. In patients with higher CD4 cell counts,
clinical followup and trials of antimotility drugs are a reasonable
approach before pursuing endoscopy.
Headache
TOP
What are
the important causes of headaches in HIV-infected patients?
The causes
of headache vary according to CD4 cell count. Patients with a CD4
count of >300 cells/mm3 usually have headaches with common causes
such as muscle tension, migraine, or drug side effect. Sinusitis
is more frequent in patients with than without HIV and may cause
headaches. In patients with low CD4 counts (<200 cells/mm3) opportunistic
infections (eg, Cryptococcal meningitis, toxoplasmic encephalitis)
and malignancies (eg, CNS lymphoma) are important causes to consider.
How should
you work up patients with headache?
Patients with
CD4 counts of <200 cells/mm3 should have a contrast head CT scan
or MRI, followed by lumbar puncture if the scan does not reveal
a cause. In a study of CT scans for evaluation of headaches in HIV-positive
patients all cases with mass lesions or white-matter lesions occurred
in patients with CD4 counts of <200 cells/mm3. Serologic tests
for cryptococcal antigen and Toxoplasma titers are helpful in patients
with CD4 counts of <200 cells/mm3.
- Antiretroviral
medications are a common cause of HIV-related symptoms. Some drugs
can cause life-threatening reactions and conditions, including
hypersensitivity reaction, pancreatitis, lactic acidosis, and
Stevens-Johnson syndrome.
- The CD4
cell count and viral load are important in symptom evaluation;
symptoms associated with OIs in immunocompromised patients have
other causes in patients with intact immune function.
- Nausea and
diarrhea, very common side effects of PIs, zidovudine, and didanosine,
can be managed by switching drugs or with symptomatic therapy.
Pneumococcal pneumonia, the most common bacterial pneumonia in
persons with HIV, can occur early in the course of the disease,
before other manifestations of immune suppression. Sinus disease
is also common in persons with HIV.
Chronic fatigue requires a careful assessment to differentiate
psychological from physical etiologies so that the underlying
cause can be addressed.
- Painful
neuropathy, frequently caused by antiretroviral medications, can
also result from HIV disease. Treatment may include stopping a
drug or treating with tricyclic antidepressants, narcotic analgesics,
or gabapentin.
- Dermatologic
problems common in HIV disease include pruritus, crusted scabies,
herpes zoster, molluscum contagiosum, and seborrheic dermatitis.
- Common oral
lesions include oral candidiasis, oral hairy leukoplakia, ulcers,
and gingivitis. Common causes of oral ulcers are zalcitabine,
HSV, and aphthous ulcers.
- Wasting
may have a treatable cause, but even nonspecific AIDS wasting
can be treated with nutritional supplementation, appetite stimulants
and antiemetics.
- Myalgia,
an especially common side effect of taking a PI and a statin,
may require muscle biopsy and treatment with either an antibiotic
or IVIG or steroids if the condition does not improve after stopping
the implicated medications.
- Headaches,
common with HIV disease, may be due to a CNS infection or neoplasm
if the CD4 count is less than 200 cells/mm3.
Suggested
Resources
TOP
Graham CB,
Wippold FJ, Pilgram TK, Fisher EJ, Smoker WR. "Screening CT
of the brain determined by CD4 count in HIV-positive patients presenting
with headache." Am J Neuroradiol. 2000; 21:451-454.
Health Care
and HIV: Nutritional Guide for Providers and Clients. 2002.
Rockville, MD: Health Resources and Services Administration. Available
at http//:www.aidsetc.org. Accessed 12/03.
Penzak Sr,
Chuck SK, Stajich GV. "Safety and efficacy of HMG-CoA reductase
inhibitors for treatment of hyperlipidemia in patients with HIV
infection." Pharmacotherapy. 2000;209:1066-1071.
Cases
TOP
1.
A 45-year-old HIV-positive man, last CD4 count 150 cells/mm3,
comes to see you reporting aching in his right arm for 3 weeks.
It began with only mild tenderness, but in the last week has become
more painful and seems swollen. He is on ART with zidovudine (AZT),
efavirenz (EFV), and nelfinavir (NFV). He is taking atorvastatin
for hyperlipidemia. On physical exam, he is febrile, and his right
arm is edematous and radiating heat without erythema. You obtain
a CPK level which is normal.
Question:
What is the most likely diagnosis?
Answer:
This patient has symptoms and signs of infectious myositis or pyomyositis,
which usually develops insidiously over 2-3 weeks. In the first
phase of infection, the involved muscle is tender with mild swelling.
After 2-3 weeks a second phase manifests, usually with fever and
edema, heat, and painful induration of the involved muscle. Erythema
over the muscle is usually not seen. Laboratory values are usually
notable for a lower than expected CPK but may include an elevated
sedimentation rate and leukocytosis. Zidovudine-induced, statin-induced,
and HIV-associated myopathy are less likely, as CPK would be elevated
in these disorders, and the symptoms and signs in this patient are
localized to one muscle group. Confirm the diagnosis of infectious
myopathy with ultrasound or CT or MRI scanning, which will show
a purulent abscess in the involved muscle. Blood cultures are not
useful. If not treated, septic shock often ensues.
Question:
What is the most likely cause?
Answer:
Most cases of infectious myositis are due to infection with Staphylococcal
aureus. Other organisms reported have included Streptococcus, Toxoplasma
gondii, cytomegalovirus, Microsporidia, Cryptococcus neoformans,
Mycobacterium avium intracellulare, Salmonella, Nocardia, and gram-negative
organisms.
2.
A 37-year-old man with Category 3 HIV disease (an AIDS
indicator condition plus CD4 count nadir of <200 cells/mm3),
last CD4 count 350 cells/mm3,
comes to your office complaining of fatigue, nonspecific abdominal
pain, nausea, and vomiting for the past 12 days. Review of systems
is otherwise negative. He takes stavudine (d4T), zidovudine (AZT),
and nelfinavir (NFV) as ART and fluoxetine for depression. On physical
exam, his temperature is 37.9 degrees, respiratory rate is 25, abdomen
is diffusely mildly tender to palpation, with increased tenderness
in the right upper quadrant, no signs of jaundice, guaiac is negative.
Question:
What is the differential diagnosis of causes related to ART?
Answer:
The differential diagnosis of ART-related etiologies in this case
should include pancreatitis, based on symptoms of abdominal pain,
nausea, and vomiting in a patient taking stavudine, although pancreatitis
usually presents more acutely with more severe pain. Hepatitis should
be considered with these symptoms in patients taking PIs. Lactic
acidosis should always be suspected in a patient with these symptoms
taking a nucleoside.
Question:
What initial lab work should be ordered?
Answer:
Initial lab work may include CBC, basic metabolic panel, liver panel,
amylase, lipase, lactate level, and coagulation studies. In the
case of this patient, the lactic acid level was elevated. Further
support for the diagnosis of lactic acidosis would include an increased
anion gap, decreased bicarbonate, and elevated aminotransferases,
lipase, amylase, CPK, and LDH.
|