GENERALIZED/INJECTION SITE REACTIONS

PATHOPHYSIOLOGY

Transient and mild cutaneous reactions related to interferon treatment occur in 10% of

patients,1 and these are reported much more frequently than local injection-site reactions.2

Generalized skin rashes, alopecia, and psoriasis are more common cutaneous reactions

associated with interferon.2

Possible explanations for this type of skin eruption include:

· Interferon acting as a biologically active substance in the skin (infiltration of skin

eruptions with lymphoid CD4 cells)

· The development of an immune complex, which is trapped by the skin and formed by

the pre-existing antibody to specific viral antigen, and the antigen being released by

the interferon

· The expression of adhesion molecules by the vascular endothelial cells in the skin

may result in skin eruptions.3

Other factors that must be considered when investigating the etiology of cutaneous

reactions include conditions that may predispose a patient to cutaneous ulcerations

(eg, allergies, infections, injection-site technique, location, reaction to a drug excipient,

injecting drug that is cold, interaction with concomitant medications, and a local reaction

to antiseptic used to clean the skin).2 In cases of cutaneous reaction occurring during

treatment with interferon, either alone or in combination with other agents, identification

of the etiologic agent may be unclear. Injection-site reactions, induration, or necrosis

appear to be extremely rare side effects of standard interferon,2 but injection-site

reactions may be more common with peginterferon. Injection-site reactions usually

present as erythema and rarely involve induration at the injection site.4

Several theories have been postulated regarding the etiology of cutaneous necrosis or the

development of ulcerations at the injection site. Theories include:

• A local immune-mediated inflammatory process in the skin.5

• Direct toxic effect of interferon.1

• Peri-arterial or intra-arterial injection (congestion disrupting blood flow), with

subsequent cutaneous infarction.5

• Overproduction of inflammatory cytokines, such as tumor necrosis factor and

interleukin-6, in the subcutaneous tissue resulting in hyperpermeability of the cutaneous

vasculature.6

GENERAL MANAGEMENT STRATEGIES

1. Perform thorough skin assessment at baseline, prior to initiation of therapy, and at

regular intervals thereafter.2 Nurses should instruct patients to monitor their injection

sites for the development of erythema and to report this finding immediately.

Side Effects Management Handbook • V. Cutaneous: Skin, Hair, Nails • p. 7

2. Assess and monitor all patient complaints.2 Once erythema is noted, have patients

avoid injecting around/at the erythematous area.

3. Pay attention to injection sites, noting reports of unrelieved pain, erythema,

discoloration, induration, swelling, or the development of lesions or eruptions.2

4. Be aware that hypersensitivity can develop at any time.

5. Rule out AI and extrahepatic manifestations of hepatitis C, such as porphyria cutanea

tarda or lichen planus, as etiology.

6. Rule out coinfection-related skin infections and sequelae.

7. Therapy may need to be discontinued for severe psoriatic flare or due to severe grade

3 skin reaction. In some cases, therapy may be reinstituted on resolution of skin

reaction.

TREATMENT STRATEGIES

Pharmacologic Interventions2

1. Evaluate drug (eg, cloudy color, excipient added to product).

2. Advise patient to make sure injection solution is at room temperature prior to

injection and to inject drug more slowly.

3. Assess subcutaneous technique (bevel up, site rotation, etc).

4 Recommend application of cool or warm compresses to site before and after

injection or aloe and lidocaine gel as needed. For injection pain: topical analgesics

(eg, lidocaine and prilocaine [Emla® cream]), oral analgesics.

5. Give topical povidone-iodine cream (Betadine®) or topical mild corticosteroid creams

for rash, reactions, and drug-related pruritus.

6. Premedicate with diphenhydramine (Benadryl®) before peginterferon to decrease

potential of an allergic-type reaction. H1 blockers are better for prevention than

treatment. Interferon’s activation of macrophages/neutrophils can lead to

degranulation and enzyme release, resulting in lytic action on nearby cells.

Basophils/eosinophils are 10% histamine; if lysed, histamine can be released into the

system (as seen in hives). A nonsedating antihistamine should ideally be used.

7. Give hydroxyzine (Vistaril®) or naltrexone (Depade®) as needed.

8. Increase dose of oral antihistamine at bedtime if taken for pruritus.

9. Prescribe antibiotics if pruritus is secondary to infection, cellulitis, etc.

10. Assess for use of concomitant medications, herbal therapies, or vitamins that may

also cause skin reactions (eg, St. John’s wort may cause photosensitivity).

11. Dose reduction or drug holiday; restart when clear using antihistamine premedication;

rechallenges are often successful.

Nonpharmacologic Interventions2

Providers should:

1. Assess onset of rash and stress to patient that sun exposure should be limited.

2. Rule out seasonal skin eruptions and AI diseases, eg, psoriasis.

3. Address fluid loss due to fever, nausea/vomiting, diarrhea, and decreased fluid intake.

4. Consult a dermatologist, if needed, to assist in determining cause of reaction, and

treatment information.

Side Effects Management Handbook • V. Cutaneous: Skin, Hair, Nails • p. 8

Patients should be instructed to:

1. Maintain good nutrition, including adequate intake of niacin and vitamin C.

2. Ensure adequate oral hydration; avoid a dry environment and use a humidifier in the

bedroom.

3. Wear sun-protective clothing and PABA-free sunscreen when outdoors for extended

periods of time.

4. Apply non–alcohol-based emollient creams (Eucerin™, Nivea™) or lotions

(Lubriderm™, Alpha Keri™, Nivea™), or cholestyramine (Questran®); usually BID

or TID.

5. Add oil at the end of a bath or add a colloidal oatmeal treatment early to the bath

(Aveeno™ oatmeal bath soaks or oatmeal bar soap).

6. Take tepid baths, which have an antipruritic effect, probably resulting from capillary

vasodilation. Limit to 30 min/d. Use mild soaps, eg, Dove™, Neutrogena™, and

Basis.™ Use Oilatum® soap for pruritus.

7. Wash clothing, undergarments, and sheets with mild soaps made for infant clothing

(eg, Dreft™).

8. Practice cutaneous stimulation: firm pressure at the site of itching, at a site

contralateral to the site of itching, and at acupressure points may break the neural

pathway. Rubbing, pressure, and vibration can relieve itching. Avoid scratching.

9. Remove tags from clothing, avoid constrictive garments, or clothing made from wool,

synthetics, or harsh fabrics/bedding for pruritus.

10. Avoid soaps and deodorants that contain scents and genital deodorants or bubble

baths.

11. Avoid alcohol-based skin lotions or petrolatum (Desitin®) or mineral oil.

REFERENCES

1. Azagury M, Pauwels C, Kornfeld S, Bataille N, Perie G. Severe cutaneous reactions

following interferon injections. Eur J Cancer. 1996;32A:1821.

2. Stafford-Fox V, Guindon KM. Cutaneous reactions associated with alpha interferon therapy.

Clin J Oncol Nurs. 2000:4:164-168.

3. Toyofuku K, Imayama S, Yasumoto S, Kiryu H, Hori Y. Clinical and immunohistochemical

studies of skin eruptions: relationship to administration of interferon-a. J Dermatol.

1994;21:732-737.

4. Cnudde F, Gharakhanian S, Luboinski J, Dry J, Rozenbaum W. Cutaneous local necrosis

following interferon injections. Arch Dermatol. 1991;30:147.

5. Shinohara K. More on interferon-induced cutaneous necrosis. N Engl J Med. 1995;333:1222-

1224.

6. Klapholz L, Ackerstein A, Goldenhersh MA, Vardy D, Nagler A. Local cutaneous reaction

induced by subcutaneous interleukin-2 and interferon alpha-2a immunotherapy following

ABMT. Bone Marrow Transplant. 1993;11:443-446.

Side Effects Management Handbook • VI. Endocrine • p. 1

 Below is some great advice off Peppermint Pattis FAQ list.

INJECTION HINTS

Wash your hands before beginning.

Take the box to where you inject, open up the box and take the vial out.

Clean the injection site with an alcohol wipe.

Wipe the vial top with an alcohol wipe also.

Now its time to find out where you are gonna make a hole. The nursing term is "clean to dirty". You put the pad at the spot where you are gonna inject and using a circular motion clean from that point out a few inches.

Fill the syringe. Pull the top off the syringe. Pull the cover off the needle.

Holding the vial in one hand, have the syringe in the other and brace both hands together. The reason is to not miss the center of the vial and nick or blunt the needle.

(This part applies only to the powdered form of interferon. You can skip this paragraph if you’re using the new pre-mixed, already in the syringe stuff.) Turn the vial upside down and draw in the IF. If its real cold, or the syringe is a 29g or smaller getting the stuff in can be a problem. Let it calm down and push out the air. (vial and syringe still upside down) Then draw to the full dose, occasionally pushing out air bubbles. I draw a little more past the fill level, so if its a 3mil dose instead of the .5cc I go to a couple of small marks beyond
.5. Flick the syringe near the vial with your finger, this makes air bubbles gather and go out the needle.

Take the needle out of the vial.

Holding the syringe upside down, push the plunger to the correct level (ie .5cc) this gets rid of any air in the needle.

With one hand pinch the skin/fat layer at the injection site.

As fast as possible push the needle into the layer with the syringe almost parallel to the skin (hold the syringe similar to the way in which you hold a pencil). The faster the needle goes in the less pain there is.

Very slightly pull back on the plunger to check for blood. If the syringe fills with blood, it means you’ve hit a vein and need to start the procedure over again.

If there is no blood in the syringe, you can then push the plunger.
Pull the syringe straight back. You get less bleeding if you don’t play twister.

Drop the syringe in the sharps container.

Syringes: I’ve found that the .5cc ½ inch 29 (or 28) gauge insulin syringe to be the best. Gauges that are numbers like 24 or 22 are bigger and hurt more.

Things that happen after injection:

Sometimes there will be a tiny bit of blood after an injection.
This just means you’ve probably popped some capillaries or punctured a small vein. It’s nothing to worry about, just cover it up with a bandage and let it clot.

The day after a shot, a red area is quite normal. They can range from dime size to silver dollar size and may feel hot and tender.
A small area is fine, but if it gets much bigger and hotter, or you see
something that looks infected, contact your doctor.

Bruising is also very common after shots.

Sites: Most people use their thighs for injections. Some people find the lower abdominal area (*not* around the belly button) to be the least painful spot for injections.

Sharps containers: You should be provided with one, either from where you get your interferon (pharmacy or home delivery) or your doctor’s office. If you have a problem getting one, puncture-proof soda bottles can be used to temporarily hold the used syringes until you can take them to your doctor’s office and ask them what to do with them. If you do this enough times, eventually, someone might get the idea you need a real sharps container. If you have children and/or cats, keep your sharps container locked up. The hole is inviting to small hands
and paws.
---

Some find it helpful to numb the injection site beforehand. An icepack (or a bag of frozen peas) placed on the injection site a few minutes ahead of time will make the shot relatively painless.

To help prevent bruising, some people recommend using only half of the diluent provided (this applies to the powdered formulation only, not to the new pre-mixed syringes).
---

INJECT-EASE:

If you are having a problem giving yourself a shot, ask your pharmacist for a B-D Automatic Injector, Inject-Ease. They cost about $25.00, and are well worth every penny. You simply load the syringe into the automatic injector, place it on the injection site, and push a button. It is virtually painless, and also makes it much easier to choose a site to inject, thereby giving you more sites per thigh.
---

BRUISING AND DILUENT AMOUNTS

If you are experiencing a lot of bruising after your injections, you may find that it helps to reduce the amount of diluent used when mixing the powdered form of interferon. Schering always overfills their diluent bottles or syringes. When using the powdered form of Intron-A, you only have to use enough diluent to disolve the powder. 0.4 to 0.5cc is a comfortable volume for subcutaneous injection. The only time you need to absolutely use a known volume is when you use a 3mu vial for multiple doses and you have to know how much you put in so you know how many mu per cc and what the volume will be for fewer than 3mu a
dose.
---

 NEEDLE SIZE

Many "Interferon Rangers" recommend not using the syringe that comes with your interferon prescription, for the actual injection. Use that one to mix the interferon powder, and buy a box of ½ cc Microfine IV 29 gauge syringes to use for the injection. The needle that comes with your interferon is a fairly large gauge and inserting it through the rubber stopper of the interferon vial dulls it a little. Using a smaller gauge needle will make the injection more comfortable, and using a separate needle to mix the diluent with the powder will
keep your injection needle sharper.
---

 HELP! I THINK I HIT A VEIN!

When giving yourself an injection, it’s recommended that you pull back slightly on the plunger, to check for blood, before actually injecting. But, occasionally people forget, and it’s almost a sure thing that at least once you will pull the needle out and find blood and bruises. Unless you are injecting into your neck and hit the jugular you have no problem! And even then, with the size of needles we use, it would be real hard to have a bleeding problem. The skin is "rich" with blood supply, so its just a matter of time before you "nail" something that
bleeds or shows up as a bruise (not just the normal interferon reaction).

Normally, if you hit an actual vein, there will be no doubt in your mind, as the blood tends to come up into the needle very quickly. If you see that happen before you actually inject, just start over again with a fresh dose. If you only see bruising or a small drop or two of blood, chances are that you only went through some capillaries and it’s nothing to worry about. The only important thing to do if you are bleeding after an injection is to cover it with a band-aid. Even for long-term interferon users there is enough clotting factor to stop the bleeding in a few minutes. The band-aid is to stop making a mess. Interferon is given intramuscularly and intravenously for other
conditions, so even if you are "lucky" enough to find a real vein or vessel the interferon won’t hurt you.
---

Some people say it is not necessary to discard the dose. The caution against injecting the interferon intravenously is because interferon is very irritating and can cause a slight phlebitis (inflammation of the vein). Also it will be painful once the reaction starts, with swelling and redness. If that ever happens to you first apply cold compresses to keep the swelling down and take your favorite painkiller. If after 24 hours the swelling becomes worse, along with increased pain and redness, apply warm compresses and call your doctor or go to the emergency room.
---

Question: (11/26/01)
I have been giving myself my Peg-Intron injections intramuscularly, and not just immediately under the skin and its fat layer. I know the medical guide officially instructs for a subcutaneous injection, but every time I've done so, the medicine seeps out, or even squirts back out, as I have no real fat layer under my skin. (Yes, I'm quite thin.) Does it really matter, so as long as I don't inject into a blood vessel? I DON'T wish to lose my medicine by seeing it seep back out.

Answer by Brian Boyle, MD
Dr. Boyle is an attending physician at the New York Presbyterian Hospital-Cornell Medical Center and Assistant Professor of Medicine in the Department of International Medicine and Infectious Diseases at Weill Medical College of Cornell University.

Injecting Peg-Intron in the muscle may alter its delivery to some extent, although I am unaware of any data that establish how significant that alteration would be and whether or not it is likely to be clinically significant. In addition to potential alterations in drug pharmacokinetics, however, intramuscular injections also carry other risks, including infection. If at all possible, you should try to stick with the injection procedures the company recommends, since this is how the drug was studied. You should discuss your problems with identifying suitable sites with your doctor and try to find sites for injection (for example, the thigh or upper arm) that will work for you. Of course, these should be rotated so that you're not always injecting into the same area. Also, injection technique may be a problem as well and your doctor (or the nurse) can give you some instructions on that as well.

This injection site map can be printed out and used to help make injecting interferon easier. Start numbering the injections you give yourself and write the number in each square. This will help you to properly rotate your injections so the same spot isn't used more than once every 6 or 7 weeks

ALSO: If you are on Pegasys Please see

Pegasys: Injection Guide

Insomnia

It seemed the longer I was on treatment, the harder time I had sleeping. I would fall a sleep but quickly awaken an hour later. I found caffeine, and interferon did not mix ! When I stopped using it all together, I found most of my sleeping problems were diminished. Although many people I have talked to need medication. When I took a regular strength Tylenol PM  it seemed to relax me, just enough to sleep. But again, ask your doctor his thoughts on Tylenol. Many of my friends thought Ambien worked for them. Do not suffer with sleepless nights, tell your doctor, and get some help.

INSOMNIA

PATHOPHYSIOLOGY

Insomnia is defined as the prolonged inability to sleep.1 Cytokines function primarily as

communication signals for the immune system, but cytokine receptors are present on

many cell types within a variety of organs, including the brain.2 The cytokine receptor

sites located within glial cells, astrocytes, and the brain stem reticular formation result in

biochemical and functional changes that affect sleep-inducing substances, such as

prostaglandin D2, factor S, serotonin, and IL-1. It is important to note that insomnia is a

common symptom of depression. Significant depletion of serotonin levels will manifest

in a variety of CNS symptoms, including depression and insomnia.2 Insomnia as a result

of decreased serotonin levels is seen with interferon therapy.

TYPES OF INSOMNIA1

· Initial: Difficulty in falling asleep.

· Intermittent: Inability to stay asleep.

· Terminal: Early morning awakening.

ASSESSMENT3

1. Pretreatment assessment of physical, psychological, and psychiatric causes of

insomnia.

2. Physical assessment includes the presence or persistence of pain, dyspnea, hypoxia,

cough, fever, sweats, pruritus, nocturia, polyuria, diarrhea, or urinary or fecal

incontinence.

3. Psychological and psychiatric assessment include the presence or persistence of

anxiety, depression, psychosis, mania (common with former or current injection drug

users), confusion, or dementia.

4. Assess for the presence of drug-related insomnia: corticosteroids, cocaine, caffeine,

xanthines, amphetamines, adverse reaction to diphenhydramine (Benadryl®) or

ephedrine (rebound insomnia).

5. Determine if pretreatment and withdrawal of drugs are causing insomnia

(benzodiazepines, barbiturates, alcohol, and nicotine).

6. Rule out sleep apnea; sedative agents in patients with untreated apnea can increase

sleep disorders and cause nighttime hypoxia.

TREATMENT STRATEGIES

Nonpharmacologic1:

Providers should determine whether insomnia may be due to anxiety or depression and

treat accordingly. They should also advise patients to:

1. Adhere to a sleep hygiene regimen, including regular sleep-wake patterns, and no

stimulants.

2. Consider daytime administration of peginterferon injection.

Side Effects Management Handbook • X. Neurologic/Ophthalmologic • p. 9

3. Decrease noise and other sensory stimulation at bedtime. Encourage relaxation

several hours prior to retiring for the evening (music, reading, crafting, warm bath).

4. Reserve bed for sleeping and sex. Take the television out of the bedroom.

5. Ensure bedroom is a comfortable temperature, neither too warm nor too cool.

6. Decrease fluid intake at bedtime to avoid nocturia. (Hydration during

peginterferon/ribavirin therapy is essential; however, hydration requirements

should be completed before 6:00 PM).

7. Consider massage or keeping a journal.

8. Develop an appropriate exercise regimen, but avoid strenuous exercise within 4 to

6 hours of bedtime.

9. Modify diet to avoid heavy meals and caffeine at bedtime. Include foods rich in

tryptophan (turkey, salmon, warm milk, and eggs) in order to increase plasma free

levels of tryptophan, which is a precursor to serotonin.

Pharmacologic4:

(See also “Pharmacologics” table below.)

1. Vitamin B12 and B complex have been helpful in relaxing the patient and promoting

deep restful sleep.

2. Inositol (a folic acid analogue) also enhances REM sleep and is often given with the

B vitamins in patients with vitamin B deficiency.

3. Diphenhydramine (Benadryl®) 25 to 200 mg QHS. Use with caution in patients with

cognitive impairment.

4. Trazodone (Desyrel®) 25 to 400 mg.

5. Hypnotics: zolpidem (Ambien®) 5 to 10 mg is recommended in individuals with

hepatic insufficiency. As with all hypnotics, administration is best just before

bedtime. Unlike diphenhydramine (Benadryl®), it does not contribute to next day

sluggishness in some patients (eg, “the morning after hangover”).

6. Zolpidem (Ambien®) 5 to 10 mg with diphenhydramine (Benadryl®) 25 to 200 mg.

7. Low-dose (7.5–15 mg) mirtazapine (Remeron®). Note: lower doses are more

sedating.

8. Benzodiazepines (lorazepam [Ativan®], oxazepam [Serax®], temazepam [Restoril®],

and clorazepate [Tranxene®]) can be used for simple sleep disorders because they are

safe and effective for at least 1 month of regular use and because they are able to

produce a more natural sleep (through less disruption of REM sleep). They are also

helpful in increasing the duration of sleep. Note: these drugs may be habit forming.

9. TCAs and serotonin mediators (amitriptyline [Elavil®], nortriptyline [Pamelor®,

Aventyl®], and doxepin [Sinequan®]) can be used for depression with concomitant

sleeplessness. They have a positive impact on suppression of REM and decrease the

number of awakenings from sleep.3

10. SSRIs, SNRIs, and serotonin antagonists are first-line treatment for depression

associated with insomnia. They generally prevent disruption of the sleep cycle,

although a few patients report vivid dreams that disturb sleep.

11. Quetiapine (Seroquel®) 25 to 100 mg. Consider when other options have failed.

Side Effects Management Handbook • X. Neurologic/Ophthalmologic • p. 10

REFERENCES

1. Miakowski C. Oncology Nursing: An Essential Guide for Patient Care. Philadelphia, Pa: WB

Saunders; 1997:98.

2. Licinio J, Kling MA, Hauser P. Cytokines and brain function: relevance to interferon-a-

induced mood and cognitive changes. Semin Oncol. 1998;25(suppl 1):30-38.

3. Page MA. Alteration in comfort: sleep pattern disturbance. In: Guidelines for Oncology

Nursing Practice. 2nd ed. Philadelphia, Pa: WB Saunders; 1994:148-154.

4. Riley MR, et al, eds. Drug Facts and Comparisons: 2000. 54th ed. St. Louis, Mo: Facts and

Comparisons; 1999.

Question:
My husband is on peg intron/rebetol therapy. He is in his 3rd month. The symptoms he is having are getting worse and not better. He has a tingling all over his body and especially his tongue. If he eats anything with salt in it,it gets way worse. He also has lots of chills. He does not see how he can go on this way.

He also has to take two very strong sleeping pills and a muscle relaxer in order to get a few hours of sleep per night. The medicine just makes him feel nervous and makes it impossible to sleep. Have u ever heard of these side effects? His Dr. doesn't seem to have heard of anyone having a tingling sensation like he has. I was wondering if it is an allergic reaction to the medication. Thank you in advance for your help. Please advise.

Answer by Douglas Dieterich, MD
Dr. Dieterich is Chief of Gastroenterology and Hepatology Cabrini Medical Center Assoc. Prof. of Medicine NYU School of Medicine

This is an unusual constellation of symptoms. I might advise trying an antidepressant to try to calm his nerves during the day. We have the best luck with Celexa and Paxil for this. The muscle aches and pains can be treated with and NSAID like Relafen and I would try something like Elavil or preferable Nortriptyline to sleep, because it may relieve some of the muscle pains and tingling too. I have not heard about the salt issue, but he might also want to ask his MD to check his PCR now, because if it has not gotten better by now, it may be time to stop.
 

DG DISPATCH - APSS: Sleep Disturbances Found In Patients Taking Common Hepatitis C Treatment

LAS VEGAS, NV -- June 19, 2000 -- Daytime sleepiness and disturbed nocturnal sleep are common in patients with chronic hepatitis C treated with concomitant interferon alpha-2b plus ribavirin, according to data presented at the 14th Annual Meeting of the Associated Professional Sleep Societies.
Dr. Cinda H. Clark and associates at the University of Texas Medical School in Houston used the Epworth Sleepiness Scale (ESS) and the Sleep Quality Profile (SQP) to determine the frequency of sleep disturbances in 57 patients who had been receiving interferon alpha-2b plus ribavirin for five to six months for chronic hepatitis C. The ESS measures daytime sleepiness, and the SQP measures symptoms of nocturnal sleep disturbances.
All subjects had compensated liver disease but no concomitant uncontrolled illnesses. None was HIV-positive.
While various studies have reported insomnia in 20 to 39 percent of patients receiving interferon alpha-2b plus ribavirin therapy for chronic hepatitis C, the investigations did not quantify or characterize the nature of the reported insomnia, Dr. Clark said.
Results showed that the mean ESS score was 9.6, and 22 (54 percent) patients had scores greater than 10, indicating daytime sleepiness. Six (15 percent) had an ESS score greater than 16, indicating extreme daytime sleepiness. Of patients with an ESS score less than 10, symptoms of insomnia predominated.
The mean SQP score was 4.7. Twenty-seven (66 percent) patients reported at least three symptoms of disturbed sleep. In addition, 77.5 percent were tired and unrefreshed when they woke up, 75 percent had restless sleep, and 72.5 percent reported arm or leg movements during sleep.
The data also showed that 55 percent of patients snored, 57.5 percent had difficulty sleeping at night, 20 percent woke up gasping or choking during the night and ten percent had witnessed apneas.
Dr. Clark added that further studies using polysomnography and multiple latency sleep testing are needed to confirm and characterize these sleep disturbances.

http://forums.delphiforums.com/friendship7/messages

Before I learned of my Hepatitis C I had that "bruised feeling" in my right side. And that's exactly what I thought it was... a pulled or bruised muscle. Felt it for the whole summer but never worried about it.

When I spoke with my gastro in 99 and asked him about it, he said they didn't know what it was from. Only that he had many patients that complained about this pain. Once on tx (combo) about 6 months later the pain was completely gone. Even though I was a non responder to tx, this dull pain remained gone for another 4 months. It returned after those 4 months. With added stress in our lives, the pain is worse at times. And it's turned into the sharp stabbing pain. Being on the Peg w/ riba now for 20 weeks now (I think) the sharp pain has lessened. Don't feel it every day ... sometimes it gone for a whole week. Depending on my stress level or activities.

I learned from the chat rooms that it was from our livers being enlarged and pushing on what's around our livers. Someone said it was the "sack with membranes" around the liver? Has anyone else heard of this? Thanks Patty

**This is all I could find out, about this pain on the web.

UPPER RIGHT QUADRANT (URQ) PAIN (SIDE PAIN)

Even though the liver itself contains no nerve endings, and does not feel pain, many people with HCV experience a pain on the upper right side of their body, just beneath the ribs. It varies from a dull ache and bruised feeling, to sharp stabbing pain which is quite different from “gas pains.”

This is thought by some to be “referred pain” from the swelling of the liver capsule due to the disease process. This pain may also be referred to the right shoulder or to the back between the shoulder blades.

Help from our Message boards

http://members.bellatlantic.net/~clotho/cfaq.htm#II.2.2

Hi Patty,

That's true about the liver being enlarged.. pressing against the membranes around it and that's what causes the pain. I have heard many people say their docs tell them their livers can't "feel" pain... which is of course not what you want to hear when you can feel a stabbing PAIN in your right side!!... but that's what they mean.

I can always feel certain things... coffee for one. Or if I am really run down. I'm glad it's going away for you again... and I hope it stays that way!!!!

When I was first diagnosed... and had been drinking... I had a terrible pain in my right shoulder... my whole right arm in fact. I guess "referred pain" is kind of like feeling pain in a tooth... but not the tooth that has a cavity.

Whatever causes the liver pain, it is real... and it's always a signal to me to drink lots and lots of water!

((((((((((Patty))))))))))))) Hope you are doing ok!!

Hi Patty
You said: Someone said it was the "sack with membranes" around the liver? Has anyone else heard of this?

Yes! I can put a name to that "sack" for you. :)
It's called GLISSON'S CAPSULE

Here's a couple of places that mention it

http://www-sop.inria.fr/epidaure/AISIM/simulateur/foie-gb.html
(under "structure")

http://www.ariess.com/s-crina/liver-anatomy.htm

http://medic.med.uth.tmc.edu/edprog/00000213.htm

Hope this helps! mkindly
http://forums.delphiforums.com/liverfailure
http://www.expage.com/cirrhosis

Patty - You are absolutely correct about the cause of the pain. It can occur when the liver is healing (shrinking) or swelling due to inflamation. Our internal organs do not cause pain - a damaged kidney will cause no pain but the bleeding and swelling in the surrounding area will. Your pain is not a phantom pain, it is real. It took me several docs and some personal research to find this info. but I finally found people who knew what they were talking about.

PAIN

PATHOPHYSIOLOGY

Pain is an unpleasant sensory or emotional experience associated with actual or potential

tissue damage or described in terms of such damage.1 There are many reasons that a

patient may experience the sensation of pain. Disease, treatment, or lifestyle changes may

contribute to pain. Pain affects many patients undergoing therapy for a disease state like

hepatitis, cancer, or cardiac or pulmonary disease. Uncontrolled pain can lead to a

negative response to therapy, interfere with wound healing, and can interfere with patient

treatment adherence.2 Pain can lead to depression, social withdrawal, anger, and failure to

participate in activities of daily living (ADLs), the treatment plan, and sexual activity.

Interferon therapy, with the interaction of the interferon cascade, can cause myalgias,

HA, and arthralgias, which can negatively impact patient well-being. Prolonged pain can

also interfere with a patient’s role, responsibility, and QOL.1

1. Pain can be treatment related through the activation of the interferon cascade and the

release of IL-8. The patient may experience muscle and fat breakdown resulting in

myalgias and arthralgias. The B cell immunity delayed response can cause an

exacerbation of arthritic pain. The FLS can cause muscle tightness and HA.

2. Ribavirin-induced anemia can cause chest pain and shortness of breath.

TYPES OF PAIN1

• Acute: Duration is usually <6 months; characterized in intensity as mild-severe;

cause is usually known.

• Chronic: Duration is usually >6 months; cause may or may not be known. Patient

may respond to treatment but pain may not subside after treatment cessation/healing.

Intensity described as mild-severe.

• Somatic: Most common type of pain; due to the activation of pain receptor fibers

located in cutaneous and deep tissue by mechanical, thermal, and chemical stimuli.

• Visceral: Due to the activation of pain receptor fibers located in the organs; caused

by injury, such as edema, stretching, distention, contraction, ischemia, or chemical

irritation.

• Neuropathic: Due to injury of the pain fibers at the periphery or can occur at the

central level of the spinal cord. Injury can occur from mechanical or metabolic

causes, such as spinal cord injury, nerve root compression, or metabolic neuropathy.

Neuropathic pain is less responsive to narcotics, but responds better to adjuvant

analgesics such as NSAIDs, anticonvulsants, and TCAs.

Side Effects Management Handbook • X. Neurologic/Ophthalmologic • p. 12

RISK FACTORS FOR ACUTE AND CHRONIC PAIN3

Disease States Lifestyle Related Treatment Related

· Anemia · Overactivity · Biotherapy, chemotherapy,

· Tumor necrosis · Underactivity surgery, radiation therapy,

· Tumor compression · Stress transplant

· Chronic pain · Fear · AEs and complications related

· Diagnostic tests · Use of pain for secondary gain (HA, N/V, chest pain,

· Tumor progression · Fatigue neuropathies, stomatitis,

· Substance abuse rash, infection,

fibrosis, cough, etc)

ASSESSMENT1

1. Assess presence of risk factors for pain.

a. Disease related

i. Interferon administration

ii. Stimulation of pain receptors by edema, effusions, or distention of tissue

iii. Concurrent diseases, such as arthritis, musculoskeletal disease

b. Treatment related

i. Invasive diagnostic and treatment-related procedures (surgery, biopsy)

ii. Acute complications of therapy: stomatitis, infections, inflammation

iii. Long-term complications of therapy: myopathies, fibrosis, neuropathies,

compression of nerves, nerve damage from surgery or radiation

c. Lifestyle related

i. Overactivity—some patients overdo trying to work through the symptoms of

the therapy

ii. Immobility and anxiety or stress related to anti-HCV therapy

iii. Anxiety related to the change in role and function as a result of the pain and

coping with the disease

2. Assess pain using an appropriate assessment tool, such as the 10-point Visual Analog

Scale.

3. Assess characteristics of pain; onset, location, duration, quality, frequency, severity,

associated symptoms, precipitating, aggravating/alleviating factors.

4. Evaluate types of self-care measures, impact of pain on ADLs and QOL.

TREATMENT STRATEGIES1

1. Instruct patients to institute noninvasive measures for pain alleviation, including:

a. Increase activity, force fluids, and rest if overactive.

b. Apply heat and cold to area of pain.

c. Use massage therapy, pressure, relaxation techniques, hypnosis, or guided imagery

if needed.

d. Discuss the pain and other external issues.

2. Administer analgesics

a. Nonnarcotics: work at peripheral nervous system; use as anti-inflammatory and

antipyretic. Good for mild to moderate pain. Examples: aspirin 325 to 650 mg (1–2

standard tablets) Q4H not to exceed 12 tablets in a 24-hour period. Take with food

or use enteric coated to decrease GI irritation. Acetaminophen (Tylenol®) 650 mg

Side Effects Management Handbook • X. Neurologic/Ophthalmologic • p. 13

Q4H PRN, choline magnesium trisalicylate (Trilasate®) 750 mg TID, ibuprofen

(Advil®, Motrin®) 200 to 800 Q6H PRN. New medicines like COX-2

inhibitors have been helpful in patients with arthralgias from interferon.

i. Considerations with NSAIDS4: Assess gastrointestinal toxicity, platelet

dysfunction, and renal function. NSAIDs have an analgesic ceiling; may

need narcotics once the ceiling is reached. Use with caution in patients with

thrombocytopenia, coagulopathies, asthma, and/or bleeding ulcers.

b. Narcotics: Opioids work at the level of the CNS; good for moderate-severe pain.

Patients with severe migraines may need narcotics. Consider for patients with

potential acetaminophen (Tylenol®) toxicity. Examples:

oxycodone/acetaminophen (Percocet®, Tylox®), meperidine (Demerol®),

hydrocodone/acetaminophen (Vicodin®), oxycodone (OxyContin®, OxyIR®,

Oxyfast®, Percolone®, RoxicodoneTM), propoxyphene (Darvon®), and

hydromorphone (Dilaudid®). Can use with NSAIDs if all others fail.

i. Considerations for opioids3,5: Use with caution in substance abuse patients.

Assess patient sedation, fatigue, nausea/vomiting, urinary retention,

constipation, and respiratory depression. Assess for hypo/hypertension,

bronchospasm, syncope, pruritus, and uticaria. Seven percent to 10% of

patients lack the liver enzyme CYP2D6 needed to activate hydrocodone and

codeine; patients who say the medication does not work may lack this

enzyme. Medications that impair CYP2D6 (eg, fluoxetine [Prozac®]) may

decrease the efficacy of codeine compounds. Oxycodone is not affected by

this enzyme.4

c. Adjuvant pharmacologic therapy: Antidepressants (good for use with neuropathic

pain), anticonvulsants (eg, gabapentin [Neurontin®]), psychostimulants, and

tranquilizers.

4. Consider radiation therapy or surgical interruption of nerve pathways.

5. Consider a pain management consultation if these measures are not effective.

REFERENCES

1. Clark JC, McGee R. Core Curriculum for Oncology Nursing. Philadelphia, Pa: W.B.

Saunders; 1998:80-86.

2. Curtiss CP. Assessment of pain and pain relief: key to successful pain control. Journal of

Pharmacologic Care and Pain Symptom Control. 1997;5:33-44.

3. Jacox A, Carr DB, Payne R, et al. Management of Cancer Pain. Clinical Practice Guideline

No. 9 AHCPR Publication No. 94-0592. Rockville, Md: Agency for the Health Care Policy

and Research, U.S. Department of Health and Human Services, Public Health Service; March

1994.

4. Omoigui S. The Pain Drugs Handbook. St. Louis, Mo: Mosby-Year Book; 1994.

5. Haddox JD, Joranson D, Angarola RT, et al. The use of opioids for the treatment of chronic

pain. Clin J Pain. 1997;13:6-8.