Difficult-to-Manage Lupus

Difficult-to-Manage Lupus

Having treated over 2,000 lupus patients over the last 20 years, I was intrigued when the editor of Lupus Update asked me to write about “Difficult to Manage Lupus.” After all, isn't all lupus difficult to manage? However, there are certain situations that are more difficult to manage than others. Ten patient cases are presented here:

When not to overtreat? Resistant non-organ-threatening disease?
A patient with Systemic Lupus Erythematosus (SLE) has persistently active rashes, fevers, fatigue and pain on taking a deep breath despite nonsteroidals and Plaquenil. There is no evidence for heart, lung, liver, central nervous system, hematologic or renal involvement. There are circumstances when certain treatments often do more harm than good if oral steroids or methotrexate are added in this situation, so I might try a few other things first. Consider increasing Plaquenil, consider DHEA, use very high dose nonsteroids or a local one-time only steroid boost.

Cyclophosphamide (Cytoxan) resistant lupus nephritis
Fifteen to twenty percent of all individuals with SLE have lupus in their kidneys and biopsies showing proliferative disease. With no treatment, they will be on dialysis within 2-3 years. Although Cytoxan is the treatment of choice for them, this toxic therapy does not work or wears off 30-40 percent of the time. What do I do? My options include: consider adding azathioprine (Imuran) to the Cytoxan and continue treatments; add plasmapheresis or pulse-dose steroids; or substitute nitrogen mustard for Cytoxan. Consider rebiopsying the patient and make sure that the renal lesion is reversible. Sometimes, it's better to let a patient go on to dialysis and transplant them than treat them further. Newer treatments may be utilized: cyclosporin, mycophenolate mofetil (CellCept) or tacrillimus (Prograf, FK 506). Drug trials with LJP394 and Biogen's antiCD40 ligand are available at selected medical centers.

Refractory chronic cutaneous lupus with no systemic disease
A patient has lupus rashes covering 70 percent of the body, but their ANA is negative and all blood work is normal. Plaquenil has not helped. I have had some success with: switching from Plaquenil to Chloroquine and adding quinacrine, retinoids such as Accutante or Soriatene; antileprosy drugs including thalidomide, clofazimine or dapsone; topical nitrogen mustard or BCNU.

Lifestyle-altering central nervous system (CNS) symptoms with a normal MRI scan of the brain and blood tests showing slight activity
When my patients complain about not thinking clearly, severe headaches and profound fatigue, the issue is raised as to whether it could be vasculitis of the CNS. True CNS vasculitis in SLE is usually obvious (e.g., fevers, meningitis-like picture, psychosis, seizures), and responds to high dose steroids. But could the patient have “subclinical vasculitis?” In fact, this is rare and most often the symptoms are due to abnormal blood flow to the brain due to a dysfunction of the autonomic nervous system and / or the dysfunction of chemicals known as cytokines (interleukins, interferons, etc.). I frequently order a SPECT scan (which might include antineural antibodies) and antiribosomal P antibodies and a spinal tap. Make sure that your doctor obtains LE cells, oligoclonal bands, antineuronal antibodies and IgG synthesis rate in addition to the usual determinations.

Cognitive impairment in patients without CNS vasculitis
How do we treat the patient in number 4 (above) who does not have vasculitis? Interventions are useful that improve the blood flow to the brain regulated by the autonomic nervous system (which controls the dilation or constriction of blood vessels, thus regulating our pulse and blood pressure), such as: biofeedback, relaxation techniques, cognitive therapy and counseling. Additionally, serotonin boosters (Prozac, Zoloft, Paxil) may help give a patient more energy and clarity. Antimalarials (Plaquenil, quinacrine) and DHEA can be useful. Steroids may seem to help at first but make things worse in the long run and should be avoided unless there is evidence for inflammation.

More than one miscarriage in a patient without anticardiolipin antibodies
Antiphospholipid antibodies and the circulating lupus anticoagulant can cause miscarriages. Most primary care doctors stop the workup after obtaining a negative anticardiolipin antibody and circulating anticoagulant test and don't treat the patient. On the other hand, aggressive reproductive immunologists unnecessarily treat patients with expensive and toxic approaches such as heparin, prednisone and intravenous gamma globulin for subsequent pregnancies which would be successful in any case. Active lupus by itself can cause miscarriages. I'm in the middle. I check for three to four different phospholipid antibodies, Protein C, Protein S, antithrombin III, Factor V Leiden mutation, BDRL and kaolin PTTs.

Is the muscle and joint aching a lupus flare or fibromyalgia?
Fibromyalgia can be as discomforting as lupus-associated inflammation but is made worse by corticosteroids. It is important not to inappropriately treat. I generally only treat symptoms of lupus with higher doses of anti-inflammatory medicine when there is objective evidence of joint swelling (synovitis), a high CPK (muscle enzyme), a high sed rate or CRP (blood tests for inflammation), low C3 complement or high anti-DNA. Lacking this, sometimes I have had to resort to obtaining a bone scan to assess if somebody with profound musculoskeletal discomfort and SLE is inflamed or experiencing a flare or fibromyalgia. The latter is treated with tricyclics, serotonin boosters and muscle relaxants and is seen in 25 percent of lupus patients.

The patients with non-organ threatening disease who want to treat their disease “naturally”
Twenty percent of patients with non-organ threatening disease will evolve organ threatening disease over five years, but this percentage decreases to five percent with two years of Plaquenil. No herb or spice has been shown to be specifically effective for SLE, and studies are sorely needed. None of these preparations, marketed as nutritional supplements to avoid FDA regulation, are standardized. Avoid believing testimonials and only rely on peer-reviewed published controlled studies. Let the buyer beware.

My eight-year-old daughter has aches and a positive ANA. Should I be worried?
Ten percent of women with SLE will have a daughter with the disease, and two percent a son with it. Twenty percent with SLE will have an offspring with an autoimmune disorder (most commonly autoimmune thyroid disease). Fifty percent of children of lupus patients have a positive ANA. Girls who are prepubertal develop lupus very rarely. Their positive ANA is inherited and their aches are usually due to growing pains. We usually advise against ANA or antibody testing unless there is objective evidence for a problem such as a fever, swollen joints or rash.

The 70-year-old woman with a diagnosis of new-onset lupus
Ten percent of the population develops ANAs as they age. When senior citizens are found to have a positive ANA and have a high sedimentation rate and joint aches, they often come to rheumatologists with a diagnosis of lupus. In reality, the overwhelming majority do not have the disease. Polymyalgia rheumatica, fibromyalgia, rheumatoid arthritis and particularly Sjogren's syndrome need to be ruled out.

By Daniel J. Wallace, MD, Clinical Professor of Medicine, UCLA School of Medicine. Reprinted with permission from the Maryland Lupus Foundation. Dr. Wallace is the author of “The Lupus Book: A Guide for Patients and their Families”.

=========================================================== This information is for"informational purposes" and is not meant to be used for medical diagnosis. Alwaysconsult your physician on matters such as this.