More Than Skin Deep

[Guest guest]

More Than Skin Deep - By: Geoff Drushel

Summary:

Pruritus in its most severe form can be debilitating

Story:

We’ve all experienced it – that itch we just can’t scratch. Usually, it’s in one of those really hard-to-reach places where no matter how we contort our bodies, we just can’t get there. But when we finally do, oh what relief it brings. Sound familiar? Now imagine not being able to get that relief. Imagine that no amount of scratching can stop the itch. For many people, including many with hepatitis and other liver diseases, it’s a very real problem – one that can be life-altering or even debilitating in its most severe form.

Unfortunately, the cause or causes of itch in liver disease, known medically as pruritus, is not yet known, although much has been learned about it in recent years. Fortunately, however, most itch is mild to moderate, and there are some treatments that work on a good many of those suffering from this condition. For those for whom the various treatments don’t seem to work, the research continues with an aim on developing new drugs to counter this agonizing complication.

“Pruritus can be mild, as in sporadic itching throughout the day, or it can be severe, as in interfering with one’s sleep,” says Dr. Nora V. Bergasa, a gastroenterologist/hepatologist and recognized investigator in the field of pruritus as it relates to liver disease. “It tends to be generalized, meaning it can occur all over the body. In those with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), it can present, or start, in the palms and soles.

“It is a maddening complication,” continues Dr. Bergasa, professor of medicine and chief of the hepatology division at the State University of New York in Brooklyn. “Itch, in contrast to pain, cannot be 100 percent alleviated by medical treatments at present. There isn’t a single universal treatment that effectively decreases itch. So in patients who have recalcitrant chronic itch, the impairment of quality of life is so severe that it can be an indication for liver transplantation even in the absence of liver failure.”

Pruritus, or itching, is a sensation that triggers the need to scratch. It is associated with general diseases – not just those relating to the skin – including liver disease, particularly the cholestatic type (meaning that which diminishes or stops the flow of bile, as is the case with PBC and PSC).

While it is most common in PBC and PSC, pruritus also is associated with hepatitis B and C, as well as other liver diseases. “Pruritus can be a manifestation of hepatitis C, in particular when the patient is at an advanced stage,” says Dr. Bergasa, who sees patients at Downstate Medical Center and at Kings County Hospital, also in Brooklyn. “In patients with cholestasis from PBC, the disease does not have to be advanced for pruritus to be present. It can be at any stage. On the other hand, the data tends to suggest that in hepatitis C, for example, patients who itch tend to have fibrosis and cirrhosis.”

This, she says, is in sharp contrast to hepatitis A. “The only time that pruritus is well recognized in hepatitis A is in a condition known as relapsing hepatitis A, which is a form of cholestatic hepatitis wherein patients start to recover and then relapse,” she says. “That can occur for an undetermined period of time, and the hallmark of that complication is itching.”

Crunching the numbers

All liver diseases that lead to cirrhosis are associated with cholestasis in the later courses of the disease, according to Dr. Bergasa, but PBC and PSC are conditions in which the bile ducts specifically are affected. “In contrast, there are conditions characterized mostly by hepatocellular damage like hepatitis B, C and A, except when it is relapsing hepatitis A. That’s different.”

According to Dr. Bergasa, 70 percent to 80 percent of patients with PBC will at some point itch. The fact that not every patient itches is “a mystery in itself,” she says. And while there are no prospective studies on the prevalence of itching in hepatitis C, Dr. Bergasa says that retrospective studies have suggested that at least 5 percent of patients with hepatitis C itch – low compared to PBC and PSC. “But where PBC is not a common disease, hepatitis is, so the burden of that complication can be quite substantial when you look at the actual numbers of patients affected.”

Dr. Bergasa says she believes it is the amount of liver injury that determines whether a hepatitis patient itches, not the genotype, viral load or enzyme activity. Other factors, such as age, gender, race, etc., also do not appear to have any bearing on whether a person develops pruritus.

“There are no statistics regarding hepatitis C, but, since pruritus is usually associated with cholestasis, it occurs more commonly in individuals with very advanced liver disease and jaundice,” says Palmer, M.D., a hepatologist and author in private practice in Long Island, N.Y. “There are no studies that have ever demonstrated any correlation with either genotype or viral load, and there are no studies that have correlated factors like race, sex, etc. to itching.” In other words, pruritus is an “equal-opportunity” condition.

Itch as a result of treatment from interferon/ribavirin is another matter altogether. “Itch from medication, including interferon/ribavirin treatment, is different in that it does not necessarily involve cholestasis,” says Dr. Bergasa, a principal investigator on several trials of drugs to slow the progression of liver disease in PBC. She points to the only study she is familiar with regarding itch by medication and says the results of that research indicate that approximately 11 percent of those on interferon/ribavirin therapy itch. Bergasa adds, however, that the study does not indicate whether any of the patients already were itching prior to starting treatment. Her own personal experience with patients suggests the number is lower. “It could be more or it could be less in different populations of patients and it could be even more if one could separate those with advanced disease from those who do not have advanced disease,” she says. “But I don’t really see that (in my patients). The number of my patients who itch from interferon/ribavirin is not that high – not as common (as reported).

“I think that the real incidence of itch specifically from treatment is unknown,” she adds. “There absolutely is an association between itch and interferon/ribavirin. It just may be lower than the 11 percent reported because I don’t know how many of these patients itched before they started treatment.” Many times, she says, itch from hepatitis itself is overlooked and then becomes apparent or is reported by the patient once the patient starts treatment since treatment is known as a cause of itch.

Dr. Palmer places the number higher than 11 percent for those who itch from treatment but agrees that it is difficult to know exactly what percentage of those on interferon/ribavirin therapy itch. Pruritus, she says, may occur in up to 30 percent of people undergoing combination therapy and is caused primarily by ribavirin.

While a specific cause for pruritus in general is not known, Dr. Bergasa says much has been learned about the condition in recent years. “Here’s what we do know,” she says. “We believe that as a result of cholestasis, or liver injury, substances that are normally excreted in bile are retained. And the substances accumulate in tissues, including blood. And it is believed that those substances cause the itch. The nature of this particular substance or substances, however, is unknown.”

There are many observations, she continues, to suggest that one of the reasons patients with liver disease itch is from the natural opiates our body’s opioid system creates for protection.

Dr. Bergasa says that patient perception also plays a role in itch, evidenced by the fact that not all patients with cholestasis itch or itch with the same degree. That part of the formula, she says, is not well understood and needs to be explored further. “So there are two components to this,” she says. “One depends on the liver disease, and the other depends on the patient’s perception (of itch).”

That is not to say in any way, she quickly adds, that itch is in the patients head, so to speak. “Not at all,” she says. “It is extremely real.”

Scratching an itch

Drs. Bergasa and Palmer agree that the most widely used and most effective treatment for itch in liver disease is cholestyramine (Cholestid, Questran), which is a resin that binds with iron in the small intestine. Both doctors say they have had good results with this drug and that patients appear to respond well to this treatment.

Antihistamines also are widely used, as are some antibiotics in some cases, Dr. Bergasa says. The main effect from the antihistamines, she says, is sedation. “The patient itches less because of the sedation effect associated with antihistamines.”

Dr. Palmer also recommends antihistamines to quell the itch. “Itching may be relieved by the use of antihistamines such as Benadryl or Claritin,” she says. “Either Benadryl lotion or hydrocortisone cream may be applied directly to the itchy area.”

She adds that some patients find relief using gentle anti-itching soaps and lotions. These products, made for sensitive skin, include such brands as Aveeno, Cetaphil soap and L’Occitane, as well as others containing an oatmeal base.

Treatment for dry skin, Dr. Palmer says, entails drinking a gallon of water each day in addition to using topical moisturizers. Lachydrin (ammonium lactate) 12 percent lotion tends to keep the skin well hydrated, as it helps the skin hold water. This lotion requires a prescription from the doctor. Aquaphor, an over-the counter ointment, is helpful to protect particularly dry, chafed skin and lips, she says.

Bathing or showering less often and using warm rather than hot water, in addition to using moisturizing or hydrating body lotion, will decrease skin dryness and itching, Dr. Palmer says.

Itching may occur anywhere on the body but is most common in sun-exposed areas and at the injection sites. “Pruritus frequently occurs at the site of injection of interferon,” Dr. Palmer says. “This type of skin reaction typically occurs within a day or two and may not resolve for up to a month after the injection.”

Again, Dr. Palmer recommends that a local over-the-counter topical steroid preparation such as hydrocortisone cream or Benadryl lotion be applied to the area. Also, icing the area prior to the injection may numb this region, decreasing itching. “Be sure to allow for total drying of the alcohol after cleaning the area, and do not excessively rub or touch the injection site,” she says. “It is important to keep the injection site covered from direct sunlight, as sunlight may exacerbate pruritus.

“Also try to avoid tanning salons, as this too may worsen pruritus that occurs while on treatment,” she adds. “If pain, swelling and redness accompany pruritus at the injection site, it should immediately be reported to the doctor or nurse, as it may be a sign of infection.” Dr. Palmer says that if an infection is discovered to be present at the injection site, antibiotics need to be started immediately.

It is important to protect the skin from direct sunlight. Sunbathing should be totally avoided while on therapy, as severe sunburns may occur. “A sunscreen with an SPF of 30 or more should be applied to the face and any other exposed areas prior to going outside during daylight hours,” she says. “In addition, women should wear makeup containing a sunscreen with an SPF of 15 or higher. A hat with a brim is important to wear if going outdoors between 10 a.m. and 3 p.m., and tanning beds should be avoided as well.”

Dr. Palmer suggests that a person who is prone to itching take Benadryl a half-hour before taking ribavirin. Either Benadryl lotion or hydrocortisone lotion applied directly to the itchy region usually provides relief, she says.

“Itching usually is at its worst at night, and the intensity of this symptom varies – from mild itching, which does not interfere with a person’s life, to intractable itching, which may severely interfere with normal daily activities and may be severe enough to cause a patient to discontinue therapy,” Dr. Palmer says. “In these cases, I use Medrol Dose Pac, an oral steroid (prednisone) taper, although I only use this in severe cases as steroids may elevate HCV viral loads.”

Dr. Bergasa says narcotics can be used only as a last resort, though opiate antagonists such as naloxone and naltrexone are sometimes used. Beyond these treatments, little else is left other than liver transplantation, although there are many anecdotal options some doctors may consider prior to taking that course, which is a very serious decision.

Getting out the message

“I think an important message to convey to patients is that itch can be a manifestation of liver disease,” she says. “Very often, patients attribute their itch to a skin disorder or allergy disorder and may not even mention this in the interview with their gastroenterologist or hepatologist.

“So I think one piece of information that is extremely helpful to patients is that itch can be a complication of hepatitis and that it is OK to bring it up with your doctor,” Dr. Bergasa says. “Patients need to understand that most of all, so they can get the help they need.

“In fact, a good number of people have discovered their hepatitis after seeking medical care for their pruritus,” she adds. “Unfortunately, it can sometimes take as much as a year or two before a proper diagnosis of liver disease is made.”

http://www.hepatitismag.com/storydetail.asp?storyid=158