A chronic manifestation of progressive systemic sclerosis in which the skin is taut, firm, and edematous, limiting movement.  Localized patches of linear sclerosis of the skin, mainly of the face and hands..

Scleroderma also affects the blood vessels and connective tissue of the skin, lungs, and other internal organs, causing them to turn leathery and hide-bound; losing elasticity.   The symptoms are like rheumatoid arthritis.  It occurs most often in middle-aged women.  Steroid drugs are used in treatment, but there is no cure.

Sjogren's Syndrome

Sjogren's syndrome and hepatitis C virus. Ramos-Casals M, Garcia-Carrasco M, Cervera R, Font J Systemic Autoimmune Diseases Unit, Hospital Clinic, Barcelona, Catalonia, Spain. Sjogren's Syndrome (SS) is an autoimmune disease that mainly affects exocrine glands and usually presents as a persistent dryness of the mouth and eyes. The spectrum of the disease extends from an organ-specific autoimmune disease to a systemic process. Viral infection has long been suspected as a potential cause of SS because several viruses have been incriminated in the aetiology of this disease, and a possible relationship between SS and hepatitis C virus (HCV) was postulated in 1992. In this paper, we review the literature concerning SS and HCV infection and summarise the current knowledge regarding their association and their pathogenic, clinical and immunological significances. The main conclusions of this review are that the prevalence of antibodies to HCV in patients with primary SS ranges between 14 and 19% using third-generation ELISA, chronic HCV infection may mimic the main clinical, histological and immunologic features of 'primary' SS and, finally, testing for HCV infection must be performed in patients with SS, especially in those patients with evidence of liver involvement or associated cryoglobulinaemia. HCV seems to be a rare cause of 'primary' SS in the absence of recognised liver disease or cryoglobulinaemia. Publication Types: Review

In Sjogren's syndrome, changes occur in the immune system - the body's defense against disease. In Sjogren's, the immune system lacks the usual controls. This causes white blood cells to invade glands in the body that produce moisture, such as the tear and salivary glands, and the Bartholins glands in the vagina. They can destroy the glands and cause them to stop producing moisture.
Sjogren's syndrome can also cause problems in other parts of the body, including the joints, lungs, muscles, kidneys, nerves, thyroid gland, liver, pancreas, stomach, and brain.

In people with no other health problems, the most common early symptom is the onset of severe dry mouth and eyes. In people with rheumatoid arthritis or related conditions, dry eyes and mouth develop more slowly. In this case, Sjogren's may be difficult to diagnose.

Sjogren's syndrome affects everyone differently. You may not have every symptom listed here, and you may have only minor problems with those you do have. The symptoms may seem worse at some times than at others.

Symptoms include:

Dry mouth: The mouth normally contains saliva, which aids chewing and swallowing. In people with Sjogren's syndrome, the amount of saliva is much less. This makes chewing, swallowing, and speaking difficult. It may also cause a decreased sense of taste.

Dry eyes: Your eyes may feel dry, "gritty," or "sandy." They may burn and look red. A thick substance may accumulate in the inner corner of your eyes while you sleep. Your eyes may be more sensitive to sunlight.

If not properly treated, Sjogren's syndrome can lead to ulcers of the cornea (the clear covering of the eyeball}. On rare occasions, this can cause blindness.

Swollen salivary glands: There are three set of glands that produce saliva. They're located under your tongue, in the cheeks in front of your ears, and in the back of your mouth. They may feel swollen and tender. This may occur along with a fever. This affects about one-half of people with the disorder.

Dental cavities: This is a common problem that results from a dry mouth. Saliva fights bacteria and defends against cavities. Because you have decreased saliva, your teeth may develop cavities more easily.

Dry nose, throat, and lungs: This may make your throat feel dry and tickly. You may have a dry cough, hoarseness, a decreased sense of smell, and nosebleeds. It can also lead to pneumonia, bronchitis, and ear problems.

Dryness of the vagina: This can cause painful intercourse for women with Sjogren's syndrome.

Fatigue is a common complaint. You may get easily exhausted and feel tired and worn out.

Other problems: Sjogren's syndrome can affect other parts of the body, such as blood vessels, the nervous system, muscles, skin, and other organs. This can lead to muscle weakness, confusion and memory problems, dry skin, and feelings of numbness and tingling.

Sjogren's syndrome can also affect the liver and pancreas. When it does, there is a greater chance for developing cancer of the lymph tissue. Although this is unusual, it is one reason why medical exams and continued follow-up are important.

The causes of this condition are not known. There is some evidence that viral infections, heredity, and hormones may in some way contribute to Sjogren's syndrome.

Sjogren's syndrome can affect people of any race and any age. It usually affects women. It affects more than one million people in the U.S.

Your doctor may do several things to find out if you have Sjogren's syndrome. This includes:

Physical examination: Your doctor will ask you to describe your symptoms, and will look for other symptoms, such as red, itchy eyes; swollen salivary glands; a dry, cracked tongue; and enlarged lymph glands in your neck.

Blood tests: Tests for specific blood markers can determine if you have Sjogren's syndrome. However, not everyone with Sjogren's has these markers.

Schirmer test: This helps determine how dry your eyes may be. It involves placing a small piece of filter paper under the lower eyelid to measure the amount of tears your eyes produce.

Slit-lamp examination: This is a more accurate way to find out if your eyes are dry. In this test, the doctor puts a drop of dye into your eye and examines the eye with a special instrument called a slit lamp. The dye will stain dry or eroded areas of the eye. This test is often done by an ophthalmologist (eye doctor}.

Lip biopsy: In this test, the doctor removes a few salivary glands from inside your lip. The tissue is examined under a microscope. The appearance of the tissue helps determine if you have Sjogren's syndrome.

Salivary function tests: These measure the actual amount of saliva you produce, to help determine if you have Sjogren's.

Urine tests: These may be done to test your kidney function.

Chest x-ray: This can help detect changes in your lungs.

As yet, there is no cure for Sjogren's syndrome. But proper treatment can help relieve symptoms so you can live a comfortable and productive life.

The main goal of treatment is to relieve discomfort and lessen the effects of the dryness. Since Sjogren's syndrome affects everyone differently, your treatment plan will be based on your specific needs.

Your treatment may include different ways to relieve your symptoms, such as those listed below. If you have arthritis or another condition, you will also want to follow specific treatment for that condition.

See your family doctor and your dentist regularly. Since Sjogren's syndrome can affect many parts of the body, regular checkups can help detect and prevent future problems. You may also need regular check ups with an arthritis specialist) and an eye specialist.

For dry mouth:

* Sip fluids throughout the day.

* Use sugar-free gum or candies to stimulate saliva production.

* Try saliva substitutes or mouth coating products. They may be useful in some people, and are available without a prescription.

To prevent dental cavities:

* Have frequent dental checkups.

* Use mouth rinses that contain fluoride.

* Brush and floss your teeth regularly.

* Use sugar-free products.

For dry eyes:

* Use artificial tears or eye drops to help relieve the discomfort of dry eyes. Use preservative-free products, if you apply the drops more than four times per day.

* Try lubricating ointments or small, long-acting pellets for overnight or long-lasting relief.

* Your ophthalmologist may recommend a simple operation that blocks tear drainage from your eye.

For dry skin:

* Use moisturizing lotions for sensitive skin.

* Avoid drafts from air conditioners, heaters, and radiators, when

possible.

* Use a humidifier in your house and at work.

For vaginal dryness:

* Use lubricants made specifically to help vaginal dryness. Do not use

petroleum jelly.

Medications

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) help reduce joint swelling and stiffness, as well as muscle aches.

If you have serious complications, your doctor may recommend stronger medicines.

Exercise

Mild exercise, such as walking or swimming, can help keep joints and muscles flexible. Exercise may also protect against further joint damage.

A note about pregnancy: A certain blood marker often found in women with Sjogren's syndrome can, very rarely, be associated with heart problems in newborn babies. If you're a woman with Sjogren's syndrome who is planning to become pregnant, see your doctor about testing for this marker. If it is present, ask your doctor whether pregnancy is advisable. If you do become pregnant, you and your doctor can work out the best plan to manage the situation.

Sjogren's syndrome is generally not life-threatening. The outlook for people with this condition is usually good. Dryness, however, may last for the rest of your life. By using artificial moisture and practicing good oral hygiene, you can help prevent serious problems.

If you have Sjogren's syndrome and a rheumatic disease, make sure you follow your doctor's complete treatment program.

The Arthritis Foundation

Contact your local chapter of the Arthritis Foundation for more information about Sjogren's Syndrome. The following booklets may be useful:

* Coping with Pain

* Coping with Stress

* Exercise and Your Arthritis

* Rheumatoid Arthritis

* Scleroderma

* Systemic Lupus Erythematosus

National Sjogren's Syndrome Association
3201 West Evans Drive
Phoenix, AZ 85023
1-800-395-NSSA (6772)
The National Sjogren's Syndrome Association is an international, nonprofit all volunteer organization dedicated to providing educational information to patients and health professionals worldwide. Sponsors support groups and national and regional conferences. Publishes: a national newsletter, the Sjogren's Digest; a quarterly collection of articles, Patient Education Series; and a patient guide, Learning to Live with Sjogren's Syndrome.

Sjogren's Syndrome Foundation
366 North Broadway, Suite PH-W2
Jericho, NY 11753
1-800-475-6473
The Sjogren's Syndrome Foundation, Inc. is an international organization that provides materials, educational programs, and support groups throughout the U.S. and abroad. Publishes Sjogren's Syndrome Handbook: An Authoritative Guide for Patients and a monthly Moisture Seekers Newsletter.

Skin and Hepatitis C

Hepatitis C Virus–Related Skin Diseases  
 
 
  Marie-Sylvie Doutre, MD

 

THE HEPATITIS C virus (HCV) was identified 10 years ago thanks to research in molecular biology.¹ At present, HCV infection is a major public health problem in many countries, with the worldwide prevalence of HCV markers ranging from from 0.1% to 5% (including 150 million chronic carriers). Infection becomes chronic in 70% to 80% of cases and is complicated by cirrhosis within 20 years of contamination in about 20% of them. Once the cirrhotic process has begun, the incidence of hepatocellular carcinoma ranges from 1% to 4%. Factors leading to more severe liver injury include excessive alcohol comsumption, older age at the time of initial infection, immunosuppression, and specific genotypes. During the course of HCV infection, many extrahepatic manifestations have been reported.²

 
 

IS THIS VIRUS CAPABLE OF INDUCING CUTANEOUS DISEASES?
YES, CERTAINLY.

 

Hepatitis C viral infection is clearly involved in cases of mixed cryoglobulinemia (MC) and porphyria cutanea tarda (PCT). Recent evidence has incriminated HCV in many cases that, in the past, would have been diagnosed as essential MC. This syndrome is characterized by palpable purpura, arthralgias, and general weakness associated with cryoglobulins composed of different immunoglobulins with a monoclonal component (rheumatoid factor) in type II and polyclonal immunoglobulins in type III.

Since the initial observations in 1990,³ several reports have described MC in about half of all patients with chronic hepatitis.^4-8 Patients with cryoglobulinema had cirrhosis more frequently and had a longer history of hepatitis than those without.⁹ Similarly, 50% to 90% of patients with MC had anti-HCV antibodies and liver dysfunction.

Affected patients often present with signs and symptoms of vasculitis involving one or more organ systems. An increasing number of recent reports suggest that cutaneous lesions are a major presenting feature in some patients and even lead to the discovery of occult HCV infection.¹⁰ There is a correlation between the presence of palpable purpura, the most frequent cutaneous lesion, and cryoglobulin levels. Several findings confirm that HCV is the etiologic agent for MC and that the virus may be involved in the pathogenesis of the vasculitis.¹⁰ Hepatitis C virus RNA sequences and HCV antibodies have been found in sera and cryoprecipitates, more concentrated in cryoprecipitates than in supernatants.¹¹ By immunohistochemical or in situ hybridization methods, HCV has been found in association with IgM and IgG in the cutaneous vasculitic lesions of some patients.^12-14 More often than not, type I interferons have proven effective in treating cryoglobulinemia and improving the results of liver function tests, which suggests a direct role for HCV in the development of MC.^{15, 16} On the other hand, in systemic vasculitis, as in polyarteritis nodosa, HCV does not seem to play an important role.^17-19

A very strong association (50%-90%) between sporadic PCT and HCV infection has been demonstrated in patients from the European Mediterranean basin (Italy, Spain, and France),^20-27 the United States,²⁸ and Japan.²⁹ In other countries (eg, Germany and New Zealand), the prevalence is low, indicating that there is not significant association between HCV and PCT.^{30, 31} Hepatitis C viral infection is associated with an increased severity of liver histologic changes, chronic hepatitis, and cirrhosis. Some cases of hepatocellular carcinoma complicating PCT may also be linked to HCV infection.

Yes, Probably.
 
Lichen planus (LP) is possibly associated with HCV infections. In 1991, LP was described in a patient with chronic hepatitis and HCV antibodies.³² Since then, numerous cases of LP associated with HCV infection have been published. Several studies have been performed to gather information on the prevalences of HCV infection in patients with LP. The reported prevalence of HCV infection in patients with LP show wide variations, from 3.8% in France³³ to 62% in Japan,³⁴ probably owing to the various techniques used to detect HCV: second- or third-generation assays (enzyme-linked immunosorbent assays or immunoblot assays) for the detection of anti-HCV antibodies and polymerase chain reaction for the detection of HCV RNA. Account must also be taken of the prevalence of the infection in a control population from the same geographic region.

Yes, Perhaps.
 
Various skin diseases have also been described with HCV infection: acute and chronic urticaria,^35-37 pruritus and prurigo,³⁸ and psoriasis.³⁹ However, epidemiological studies are essential to determine the real prevalence of these dermatoses in the course of HCV infection. The prospective case-controlled study of Cribier et al⁴⁰ in this issue of the ARCHIVES proves that at least in Europe, HCV rates in chronic urticaria are similar to those of the general population. 
 

HOW DOES THE VIRUS ACT?

 

In cryoglobulinemia, one possible mechanism is that antigen-antibody complexes made of viral particles and anti-HCV antibodies might be linked by IgM pentamers with rheumatoid factor activity directed at anti-HCV antibodies. Immune complexes initiate activation of endothelial cells, leading to altered vascular permeability, neutrophil infiltration, and vessel wall damage. However, the presence of a cryoglobulin does not necessarily result in vascular damage, which depends on the presence of factors of the complement in the cryoprecipitate, the physical and chemical characteristics of the antigen-antibody complex, and probably on other local and/or circulatory factors. An alternative mechanism was suggested by the findings of HCV in vascular endothelial cells. Antibodies or T cells sensitized to HCV-containing endothelial cells may initiate the process.

In PCT, HCV probably acts as a nonspecific factor that reveals the enzymatic deficit of uroporphyrinogen decarboxylase in a genetically determined terrain. The role of HCV in LP remains unclear: is it an alteration of epidermal antigenicity? A replication of virus in skin and mucosal lesions? This latter hypothesis is in fact unlikely, since treatment with interferons more often than not results in the eruption or aggravation of lesions.⁴¹

 

HOWEVER, WHY DO THESE SIGNS APPEAR ONLY IN CERTAIN PATIENTS?

 

Viral, genetic, or environnemental factors may be reponsible for cutaneous diseases associated with HCV infection only in some patients. Several reasons have been proposed.

Viral Genotypes?
 
The distribution of HCV genotypes varies according to the region studied. In most studies there is no predominance of any given genotype compared with a control population devoid of any cutaneous manifestation.⁴²

In cryoglobulins, no predominance of a genotype has been noted except in 2 Italian studies.^{43, 44} Three studies reported the genotype distribution of HCV-infected patients with LP; this was similar to that of patients with chronic hepatitis without LP.^45-47

Viral Load?
 
Quantitation of viral load by reverse-transcription polymerase chain reaction may offer a reliable marker of disease status. However, viral load does not influence the occurrence of cutaneous signs in relation to a cryoglobulin.

Genetic Predisposition of the Host?
 
Hepatitis C virus induces nonhepatic autoimmune manifestations only in susceptible individuals, particularly those carrying the HLA A1, B8, DR3 haplotypes or the DR4 allotype.⁴⁸ Recently, mutations in the HFE gene associated with hereditary hemochromatosis (Cys 282 tyr, His 63 Asp) have been associated with sporadic and familial PCT, suggesting that inheritance of hemochromatosis alleles may be a susceptibility factor for the development of the disease.^{49, 50} Hepatitis C viral infection and these mutations might synergize to produce clinically manifest PCT.

Coinfections With Other Viruses?
 
Coinfection with hepatitis B virus and HCV is frequent in PCT. Anti–hepatitis B virus and anti-HCV antibodies and/or hepatitis B virus DNA and HCV RNA were simultaneously detected in the serum of about 30% of patients.^23-26 In patients with human immunodeficiency virus, both the human immunodeficiency virus and the HCV are etiologic factors for PCT. However, HCV probably plays the major role.

Hepatitis G virus is part of RNA virus, transmitted by the same route as HCV. Some studies suggest that hepatitis G virus is not associated with extrahepatic manifestations.^40-51

When faced with leukocytoclasic vasculitis, a PCT, and probably a lichen, especially an oral, erosive lichen, the physician must look for a possible HCV infection. With other cutaneous diseases such as psoriasis and prurigo, no systematic screening is possible without further epidemiological studies, like that of Cribier et al⁴⁰ with chronic urticaria.

 
 
Author/Article Information

 
Marie-Sylvie Doutre, MD
Department of Dermatology
Haut-Leveque Hospital
33604 Pessac, France

	Itching in Liver Disease   By Nora V. Bergasa, M. D. Itching secondary to liver diseases, including primary biliary cirrhosis, primary sclerosing cholangitis, and hepatitis C, is a very difficult symptom for patients to endure and for physicians to manage. The reason why patients with liver disease itch is not known. It has been thought that some substances accumulate in the blood as a result of liver disease, causing itch. Although the nature of the substance(s) that cause itch in liver disease is not known, evidence has been accumulating over the past several years to suggest that some substances that are found normally in plasma known as endogenous opioids (e.g. enkephalins), contribute, at least in part to the itch secondary to liver disease. It has been proposed that these neurotransmitters cause itch by acting on special areas of the brain. Other substances that also accumulate in the blood in liver disease, including bile acids, may also play a role in this type of itch. There is no strong evidence, however, to support that bile acids cause this type of itch. Traditionally, the way itch has been studied has been by measuring the concentration of substances known to accumulate in the blood of patients with liver disease who itch. This method, however, has not advanced the understanding of what causes this type of itch. In order to conduct scientific investigation, investigators have to apply reliable methods that allow for the collection of information that can be analyzed and interpreted in an objective way. The need for the availability of good methods has been recognized for many years by investigators in the field of itch. In this spirit, an instrument was designed over ten years ago that allows for the measurement of the human behavior that results from feeling the sensation of itch: scratching. Several clinical trials that use this method to record scratching have been conducted. These studies have provided some insight into itching and scratching, including the demonstration that some patients scratch with a 24-hour rhythm, known as circadian rhythm. This finding has suggested further that the itch secondary to liver disease is mediated in the brain. At present there are several medications that are used for the treatment of itch in liver disease. These medications include cholestyramine, the antibiotic rifampicin, the opiate antagonists naloxone and naltrexone, and the serotonin type-3 receptor antagonist. These medications appear to decrease itching in many patients, but there is no medication that works well for all the patients. This reality underscores the need to continue to look for other medications that may relief the itch secondary to liver disease. http://cpmcnet.columbia.edu/dept/gi/itching.htm

 

THE FAMILY DOCTOR / Treating Skin Blotches From Hepatitis Virus Date: 11/4/02; Publication: Newsday; Author: Dr

THE FAMILY DOCTOR / Treating Skin Blotches From Hepatitis Virus Dr. Allen Douma Q. My sister is 43 and has been suffering from hepatitis C for some time. She has light-colored blotches on her face and is ashamed to go out because it looks so bad. - A.H., Far Rockaway   A. Hepatitis is inflammation of the liver. A common cause is a viral infection, but toxic chemicals such as alcohol can cause it as well. Hepatitis C is a viral infection and is the most common cause of liver disease except perhaps for alcoholism. The hepatitis C infection is transmitted from an infected person to an uninfected person. It is most commonly transmitted by unsterile needles shared by intravenous drug users. Hospital and clinic workers can be infected by exposure to the blood of infected patients. Transfusions with infected fluids is another cause. Transmission by sexual contact or from mother to fetus can also happen, but is not very common. Many people with acute (short-term) viral hepatitis can recover within months, with or without treatment. In fact, most of the time, medical treatment is unnecessary for acute hepatitis, although hospitalization is sometimes required. However, if the acute hepatitis was caused by the hepatitis C virus, there is a much greater chance of having significant problems that may last for a long time. Symptoms can begin with a general feeling of illness, fatigue and poor appetite. A low fever and abdominal discomfort may also be seen. For acute hepatitis, bed rest is recommended as needed. Interferon with ribavirin provides some benefit about 50 percent of the time. Within a month or so, a longer-acting form of interferon should be available that decreases the number of shots needed from three to one a week. Both hepatitis and the drugs used to treat it have been reported to cause light blotches of the skin called vitiligo. However, vitiligo occurs more frequently in people with thyroid problems, diabetes, pernicious anemia or Addison's disease. This depigmentation of the skin can also be secondary to atopic dermatitis, lupus and psoriasis. Often no underlying cause is found. Although vitiligo may be an indication of a serious underlying disease, its major problem is that sometimes a person thinks he or she is cosmetically disfigured, causing serious emotional consequences. If your sister's vitiligo is caused by her treatment of hepatitis C, then stopping treatment may reverse the condition, but it also may worsen her hepatitis. Treatment of vitiligo has improved during the past decade. Several treatments used more recently include: light-sensitive drugs plus ultraviolet light (PUVA), narrowband ultraviolet therapy (UVB), and local corticosteroids plus ultraviolet light. Often these treatments do not result in complete repigmentation. Try one and, if it doesn't work well, try another one. The Family Doctor is a health education column and is not a substitute for medical advice from your physician. Allen Douma spent 12 years in clinical practice. He has written, edited and advised on numerous medical publications, including the American Medical Association's Family Medical Guide. Send questions to The Family Doctor, Discovery section, Newsday, 235 Pinelawn Rd., Melville, NY 11747- 4250. Questions cannot be answered personally.   Dr, THE FAMILY DOCTOR / Treating Skin Blotches From Hepatitis Virus. , Newsday, 11-04-2002, pp A39.

 

 

Stroke

Magazine: Hepatitis Weekly, September 9, 1996 Section: Case Reports (HCV) STROKES SEEN IN HEPATITIS PATIENTS WITH MIXED CRYOGLOBULINEMIA ---------------------------

Two cases of cerebral stroke occurring in patients with hepatitis C virus infection and mixed cryoglobulinemia are good arguments in favor of testing for these conditions in patients with unexplained cerebral ischemias. Recent reports have emphasized the association between HCV infection and mixed cryoglobulinemia. Palpable purpura glomerulonephritis. arthralgias. and cutaneous and peripheral nervous system vasculitis are the hallmarks of this disorder. "Central nervous system (CNS) disease has been reported only rarely in patients with mixed cryoglobulinemia from any cause. and no detailed descriptions of intracranial vasculopathy and cerebral ischemia due to HCV infection and mixed cryoglobulinemia are available." researcher George W. Petty and colleagues wrote ("Cerebral Ischemia in Patients with HCV Infection and Mixed Cryoglobulinemia." Mayo Clinic Proceedings. July 1996:71:671-678). "We describe two patients evaluated at our institution with cerebral ischemia in the setting of HCV infection and mixed cryoglobulemia." Patient 1, a 36-year old woman, was in otherwise good health when left parietal cerebral infarction developed, and she was found to have narrowing of the supraclinoid internal carotid artery siphon, anterior cerebral artery A1. and middle cerebral artery M 1 segments bilaterally. Subsequent evaluation revealed abnormal liver enzymes, mixed cryoglobulinemia (type Ill), hypocomplementemia and a high positive test result for rheumatoid factor. The second patient was a 35 year old woman who was referred to Mayo Clinic Rochester because of headaches and seizures. She had a history of nephritis (at age 12 years), treatment with glucocorticoids, and subsequent development of avascular necrosis of both hips. When she was 31 years old, purpura caused by vasculitis developed, and she subsequently had intermittent arthralgias. When she was 33 years old, type II mixed cryoglobulinemia was diagnosed, and she was treated with prednisone. A kidney biopsy specimen showed mesangial hypercellularity. Azathioprine was added to the therapeutic regimen because of recurrent vasculitic skin lesions. The researchers found that ischemic encephalopathy developed about the time of treatment with plasmapheresis or institution of interferon alpha (IFN-alpha) treatment (or both). Both women were found to have HCV infection using polymerase chain reaction detection of hepatitis C virus RNA. "We cannot comment on the efficacy of IFN-alpha in the treatment of CNS involvement in patients with HCV infection and mixed cryoglobulinemia," George W. Petty and colleagues wrote. "Recombinant IFN-alpha has been shown to be effective in controlling disease activity, as measured by normalization of serum alanine aminotransferase levels and histologic improvement on liver biopsy specimens in patients with chronic HCV infection. "Both of our patients were treated with IFN-alpha. In one patient (case 2), IFN-alpha had been used only for a brief period before cerebral infarction developed. Whether her neurologic improvement was related to treatment with prednisone only or whether she received some benefit from the limited course of administration of IFN-alpha is speculative. The other patient (case 1) had persistent changes of intracranial vasculopathy on brain MR angiography after being treated with IFN-alpha for four months." The authors conclude that cerebral ischemia may be the initial manifestation of HCV infection and mixed cryoglobulinemia. "HCV serologic tests and cryoglobulins should be considered in patients with cerebral ischemia of inobvious cause, particularly in young patients and in those with abnormal liver enzymes," they wrote. The corresponding author for this study is G.W. Petty, Department of Neurology, Mayo Clinic Rochester, 200 First Street, SW, Rochester, Minnesota 55905.

Systemic Lupus Erythematosus

WESTPORT, CT (Reuters Health) Jan 05 - The prevalence of hepatitis C virus (HCV) infection is higher in patients with systemic lupus erythematosus (SLE) than in healthy control subjects, according to a report published in the December issue of Arthritis and Rheumatism. Also, the usual clinical manifestations of SLE are different in patients infected with HCV, the authors state.

Dr. Josep Font and colleagues from the University of Barcelona in Spain studied the prevalence and clinical significance of HCV infection in 134 consecutive SLE patients and 200 healthy subjects.

The authors found that HCV infection was present in 11% of SLE patients and in 1% of healthy subjects. Compared with SLE patients without infection, HCV-infected SLE patients had a lower frequency of cutaneous manifestations and anti-double-stranded DNA positivity. These infected patients, however, had a higher frequency of hepatic involvement, cryoglobulinemia, and low C4 and CH50 levels.

The current study represents the largest series of SLE patients ever analyzed for HCV infection, the researchers point out. The findings also "suggest a possible link between HCV infection and SLE."

Based on their results, the investigators divided SLE patients with anti-HCV antibodies into three groups: 1) Patients with a false-positive result on the antibody assay; 2) Patients with HCV infection and "true" SLE; and 3) Patients with a "lupus-like syndrome" that may have been caused by HCV infection.

"We suggest that HCV testing should be considered in the diagnosis of SLE, especially in patients without" typical SLE manifestations, the authors state. "Conversely, patients with chronic HCV infection and extra-hepatic features mimicking SLE should be tested for the presence of antinuclear antibodies and anti-double-stranded DNA."

Systemic Lupus Erythematosus:

A systemic disease that results from an
autoimmune mechanism. Individuals with lupus will produce antibodies to their own body tissues. The resultant inflammation can cause kidney damage, arthritis, pericarditis

A selection from the Lupus Foundation Of America Newsletter Article Library
(originally appeared in Lupus News, Volume 13, Number 3)

Involvement of the liver in SLE is a frequently misunderstood complication of the disease. The liver can be affected as a result of lupus itself, as well as the medications used to treat inflammation caused by lupus. There is also a specific inflammatory disease of the liver, related to SLE, called lupoid hepatitis. This column attempts to reconcile our perceptions of what "lupus in the liver" really means.

Lupus can affect the liver in numerous ways that are delineated below:

• ENLARGEMENT OF THE LIVER, or hepatomegaly, is found in 10% of SLE patients. The liver is rarely tender unless the enlargement is so great that the capsule (or covering) of the organ is stretched. The most common cause of large livers in lupus include lupoid hepatitis, congestive heart failure, or cirrhosis.
• JAUNDICE, in which the person's skin has a yellowish hue, is seen in 1-4% of patients with SLE. Manifested by high levels of bilirubin which are responsible for this pigmentation, jaundice results from autoimmune hemolytic anemia, viral hepatitis, cirrhosis, or bile duct obstruction (from gallstones, tumor, or pancreatitis). Occasionally, certain medications including nonsteroidal anti- inflammatory drugs and azathioprine may produce jaundice.
• HEPATIC VASCULITIS, or inflammation of the small and medium sized arteries of the liver, is extremely rare and is noted in one lupus patient per thousand. It responds to corticosteroids.
• BUDD-CHIARI SYNDROME (which is very rare) results from a blood clot in the portal veins which drain materials from the liver. Lupus patients with the lupus anticoagulant, anticardiolipin antibody, or antiphospholipid syndrome appear to be uniquely at risk for developing these clots. Additionally, hepatic artery clots may occur. Untreated Budd-Chiari can lead to ascites, portal hypertension, and liver failure. The preferred treatment of Budd-Chiari syndrome is anticoagulation (blood thinning).
• ASCITES is a term which refers to fluid in the abdomen as a result of the manufacture of this liquid by the peritoneum, or lining of the abdominal cavity. Often associated with serositis (or similar fluid being made by the pleura or pericardium which line the lung and heart), ascites causes swelling of the abdomen and is noted in 10% of patients with SLE. Usually reflecting active disease, it may be painless or painful and can be mistaken for a "surgical abdomen" resulting in unnecessary surgery. If an infection is ruled out, ascites is treated with antiinflammatory medication, gentle diuresis, and occasionally periodic drainage. Ascites also may result from liver failure or nephrotic syndrome.
• ABNORMAL LIVER FUNCTION TESTS may be found in 30-60% of patients with SLE. Blood enzyme evaluations included in routine blood panels such as the AST (also called SGPT), ALT (also called SGOT), alkaline phosphates and GGT may be slightly elevated as a result of a variety of mechanisms. First of all, nearly all nonsteroidal antiinflammatory agents, as well as aspirin, can elevate these enzymes, and lupus patients appear to be particularly susceptible to this. These minor abnormalities are usually of little consequence and I ignore them unless they are greater than three times normal. Also, active lupus can elevate these enzymes. Most nonsteroidals can be stopped for a week or two and the enzymes rechecked. If they remain increased, the possibilities for this elevation include hepatitis, infection, biliary disease, alcoholism, or active lupus.

This leaves us with the most perplexing problem to discuss: lupoid hepatitis. Described by Joske and King in 1955 and named by Mackay in 1956, lupoid hepatitis has undergone many changes in definitions. The overwhelming majority of patients who were told they had lupoid hepatitis between 1955 and 1975 would not fulfill current criteria for this disease. Initially thought of as the presence of chronic active hepatitis (hepatitis means inflammation of the liver) with LE cells, the term "autoimmune hepatitis" seemed more appropriate since few of these patients had typical clinical lupus. The development of diagnostic tests to detect hepatitis A, B, and more recently C changed our concepts of lupoid hepatitis. The current working definition of lupoid hepatitis is:

1. liver pathology consistent with chronic active hepatitis
2. absence of evidence for active hepatitis virus A, B or C infection
3. a positive ANA or LE cell prep

Even using these criteria, only 10% of patients at the Mayo Clinic fulfilled the American College of Rheumatology (ACR) criteria for SLE. Although fevers, joint aches, malaise and loss of appetite are common (as well as jaundice with itching), many of the physical findings we associate with SLE (rashes, other organ involvement) are usually absent. This is further complicated by the knowledge that lupus patients have compromised immune systems and can develop a viral hepatitis, take liver-toxic medications, and some abuse alcohol just as non-lupus patients do, which can lead to chronic active hepatitis. Thirty to sixty percent of patients with "autoimmune hepatitis", which is the term I prefer, also have antibodies to smooth muscle or mitochondria (AMA or SMA)

Untreated, autoimmune hepatitis is fatal within five years. It can respond to prednisone, steroids, alpha interferon, and azathioprine. Two of our patients have undergone successful liver transplants. We have come a long way in our understanding of liver disease in SLE and lupoid hepatitis, but it still takes a great of skill to sort out what is autoimmune versus viral versus medication related.