Michael D. Lockshin, MD

Ask the Expert

Decision-making in such young women can be difficult and among the most agonizing - for both patient and physician. It usually requires a very prolonged conversation with the patient and her immediate family, whether parents or significant other. While such women clearly need treatment - and preservation of fertility is obviously desired - it is very difficult to know the best option.

We use one of three options in these circumstances:

1. administer full-dose cyclophosphamide (with prednisone) and hope for the best;
2. administer prednisone and mycophenolate, although there is a little controversy as to whether this is as effective as cyclophosphamide; or
3. pretreat the patient with leuprolide acetate (Lupron) and administer prednisone and cyclophosphamide, although it makes young women pretty miserable and it must be continued for the full duration of treatment.

None of these options is ideal. The usual solution is number 2.

Low-dose cyclophosphamide would not be helpful. The Europeans (English and French, in separate investigations) have published on “low-dose” cyclophosphamide in uncontrolled trials, but their definition of low-dose is 0.5 g per meter squared every two weeks, rather than the NIH protocol of 1.0 g per meter squared every month - so I don’t get the point of it all. It seems to me the total cyclophosphamide dose is more or less the same, and they have provided no additional data regarding fertility or other critical information.

See the complete article on the Hospital for Special Surgery’s web site

Ask the Expert
Michael D. Lockshin

Several aspects of psoriatic arthritis make it hard to answer questions about its treatment succinctly.

First, there are at least three forms of psoriatic arthritis: in some patients it looks very much like rheumatoid arthritis, in others like ankylosing spondylitis, and in still others only the end joints of the fingers (and, usually, the fingernails) are involved. What may work for one type of psoriatic arthritis may not for another.

Second, although most doctors think all inflammatory rheumatic diseases are autoimmune, it has been very hard to identify specific problems with the immune system in patients with psoriasis or psoriatic arthritis. Since most treatments for autoimmune disease change the function of specific parts of the immune system, it is hard to know which function to identify as a potential target when you are not even certain that the immune system has gone awry.

Third, compared to rheumatoid arthritis, psoriatic arthritis is fairly uncommon. It is an ‘orphan’ disease, and most treatments that are tried have been borrowed from another disease rather than specifically developed for psoriatic arthritis.

That said, much has happened in the last few years. For at least the past two decades, the standard treatment for psoriatic arthritis has included nonsteroidal anti-inflammatory drugs, sulfasalazine and, in more severe cases, methotrexate or cyclosporin. Corticosteroid drugs such as prednisone have not been very effective. Methotrexate, the most effective, has the added advantage that it treats the skin condition as well as the joints, but even with it many patients failed to respond well. Drugs useful in treating the skin disease, such as acitretin (Soriatane), sometimes work in refractory cases but are often toxic.

About 5 years ago the dramatic success in rheumatoid arthritis of the new class of drugs called biologics, specifically inhibitors of a small chemical called tumor necrosis factor alpha led to trials of these drugs in psoriatic arthritis. In brief, TNF alpha inhibitors — etanercept (Enbrel) and infliximab (Remicade) - work extremely well in many patients with psoriatic arthritis of all three types[1],[2],[3]. Adalimumab (Humira) is a very recently released similar drug that may be expected to work as well. These drugs may work by inhibiting TNF alpha or by breaking the inflammatory cycle in a different way. TNF alpha inhibitors also appear to protect bone from being eaten away[4]. In clinical trials, these drugs reduce inflammation and prevent deterioration over several years, and they improve skin disease as well.

As a result of success with TNF alpha inhibitors, other biologics, which have different effects on the immune system, are now under trial[5],[6],[7]. The down side is that all of these drugs are extremely expensive, that they are injectable rather than available in pill form, and that their major side effect is that they make recipients susceptible to certain kinds of infections. Otherwise they are not particularly difficult to take. Specific information about these drugs can be found elsewhere on this website.

The details of how these biologics affect the immune system is less important than the fact that they do work in psoriatic arthritis. In doing so, they teach us that the immune system is abnormal in psoriatic arthritis, that very specific abnormalities can be corrected, and that the development of treatments based on an immunological theory of this disease is valid. Thus, in the next several years, we can expect to see many more immunologically active drugs - largely biologics - developed for and tried in psoriatic arthritis. With luck, one or more of the new drugs will be inexpensive, orally administered, side-effect free, and possibly even curative.

See the complete article on the Hospital for Special Surgery’s web site
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[1] Braun J, Sieper J. Role of novel biological therapies in psoriatic arthritis : effects on joints and skin. BioDrugs. 2003;17(3):187-99.

[2] Anandarajah AP, Ritchlin CT. Etanercept in psoriatic arthritis. Expert Opin Biol Ther. 2003 Feb;3(1):169-77.

[3] Yazici Y, Erkan D, Lockshin MD. Etanercept in the treatment of severe, resistant psoriatic arthritis: continued efficacy and changing patterns of use after two years.Clin Exp Rheumatol. 2002 Jan-Feb;20(1):115.

[4] Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. J Clin Invest 2003 Mar;111(6):821-31. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003 Mar;111(6):821-31.

[5] Kraan MC, van Kuijk AW, Dinant HJ, Goedkoop AY, Smeets TJ, de Rie MA, Dijkmans BA, Vaishnaw AK, Bos JD, Tak PP. Alefacept treatment in psoriatic arthritis: reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis. Arthritis Rheum. 2002 Oct;46(10):2776-84.

[6] Utset TO, Auger JA, Peace D, Zivin RA, Xu D, Jolliffe L, Alegre ML, Bluestone JA, Clark MR. Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.J Rheumatol. 2002 Sep;29(9):1907-13.

[7] McInnes IB, Illei GG, Danning CL, Yarboro CH, Crane M, Kuroiwa T, Schlimgen R, Lee E, Foster B, Flemming D, Prussin C, Fleisher TA, Boumpas DT. IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis. J Immunol. 2001 Oct 1;167(7):4075-82.

Special Report
Michael D. Lockshin, MD

1. ANA,FANA (Fluorescent)-Anti-Nuclear Antibody
2. Anti-DNA
3. anti-Sm antibody-_Antibody to the Smith antigen
4. anti RNP-Antibody to the Ribonucleoprotein
5. anti-Ro,(=anti-SSA(=anti-Ro))
6. anti-La,(=anti-SSB)
7. Complement,CH50,C3,C4
8. aCL, aPL, lupus anticoagulant
9. BUN (Blood Urea Nitrogen)
10. Urinary protein, proteinuria, albuminuria
11. Platelets- blood cells that aid in clotting.

Are you confused by the names of the blood tests doctors use to diagnose or monitor lupus? Do you know what the tests mean? If you are confused, perhaps the information below will help. In looking at the following information, remember:

An antibody is a protein (such as gamma globulin and other globulins) that the body normally makes to defend itself against bacteria (germs), viruses, and other things that cause harm. In lupus, the body mistakenly makes antibodies against a person’s normal tissue.

An antibody is named according to the substance (antigen) which it is made to fight. Thus, an antibody induced by a polio vaccination is called anti-polio virus antibody.

Because the basic abnormality of lupus is an immune system that is in overdrive, most of the tests measure the degree to which the immune system is active.

Other tests measure the function of specific organs such as the kidneys.

A lot of these tests and names are confusing. Don’t worry about such designations as mg/dL (milligrams per deciliter). These are technical terms that refer to a specific way of measuring one or another substance. Some laboratories use international units (IUs); some laboratories report the results of chemical tests in mols instead of milligrams. I’ve given the measurements that are most often used. If your laboratory reports your results in a different way, ask your doctor to explain which units are used and what is normal for that laboratory. I have not given numbers for tests that are either reported as positive/negative, or in cases where there are too many ways of reporting to summarize briefly.

Keep in mind that the statements above are just rough guides. There are always exceptions to every rule. I’ve listed the most common tests and the most common uses, but they may differ for you. If you are still confused, or you are in doubt, ask your doctor for an explanation.

Test: ANA, FANA (Fluorescent) - Anti-Nuclear Antibody
What test is for: An antibody against the nucleus, or central controlling part of each cell. All organs are made of cells and all cells have nuclei. ANAs have four basic patterns describing the way they look under the microscope. The patterns are “diffuse” (the whole nucleus lights up), “peripheral” or “rim” (only the ring around the nucleus does), “speckled” and “nucleolar” (two very specific spots light up).

What a positive test means: Almost all patients with lupus have a strongly positive test (still positive even when diluted more than 100 times, commonly expressed 1:100). Many normal people also have positive tests, usually less strong (1:10-1:30). The “diffuse” and “speckled” patterns are common in lupus, but are also seen in other diseases and normal people. The “peripheral” pattern is relatively specific for lupus. The “nucleolar” does not often occur in lupus. A positive test means lupus is a possible diagnosis.

What a negative test means: A negative test usually means that a patient does not have lupus, or that lupus is in remission. However, most patients in remission do not have negative ANAs. …

See the complete article on the Hospital for Special Surgery’s web site