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Central Nervous System Involvement in SLE:
Studies revealed that is possible for systemic lupus erythematosus to affect the nervous system. Patients with lupus may experience confusion, difficulty with concentrating, headaches, fatigue, strokes or other signs that show nervous system involvement.
Studies suggested that the nerve tissue may be damaged when antibodies attack nerve cells or blood vessels. It is known that the nervous system requires an uninterrupted flow of blood that is needed to supply with oxygen and nutrients its tissues. When this flow of blood is slowed or interrupted, the nervous cells are unable to function normally, and there appear symptoms. The symptoms vary, depending where the tissue injury is situated. It is good to know that the nervous system contains three parts. The central nervous system comprises the brain and spinal cord, the peripheral nervous system nerve fibers that have the role to provide the skin and muscles the power needed for sensation and movement, and the third part is the autonomic nervous system that has the role to regulate spinal, peripheral nerves and to innervate the internal organs.
An inflammation of the blood vessels of the brain that appears to 10% of all lupus patients is called the central nervous system vasculitis. This disease usually requires hospitalization and high doses of corticosteroids. Some of the symptoms that appear are high fevers, seizures, psychosis and meningitis-like stiffness of the neck. If it is not aggressively managed, the central nervous system vasculitis rapidly progresses to stupor and coma.
People with mild to moderated systemic lupus erythematosus can experience the cognitive dysfunction. That is a group of symptoms that appear at about 50% of these patients, and we can mention here fatigue, memory impairment, feelings of confusion, and difficulty to express the thoughts. By taking a neuropsychological test or a test called the positron emission tomography, these symptoms can be clearly documented. It is known that cognitive dysfunction may come and go on its own, but no optimal therapy is available. Also, it is not known which is the reason for the symptoms that appear. Dealing with a cognitive dysfunction is frustrating, and often counseling a person in developing coping skills may be helpful.
About 20% of the patients having systemic lupus erythematosus experience the lupus headache. This manifests by severe headaches, is similar to migraine and can be often seen in persons who have also Raynaud's phenomenon. As a treatment, it is useful the same one used in tension headaches or migraine, and sometimes corticosteroids.
It is known that about a third of the patients having lupus can have a false positive syphilis test, a positive anticardiolipin antibody, or a prolonged clotting time test. This is known under the name of the lupus anticoagulant or the antiphospholipid antibody. About 1/9 of the patients having lupus will develop blood clots in various parts of the body, which is called the antiphospholipid syndrome. If blood clots appear in the nervous system, they can cause a stroke, and symptoms of a stroke include the painless onset of neurologic deficits without any signs of active lupus. If a stroke appears, there must be taken blood-thinning medications. We can mention here low-dose aspirin, coumadin or heparin.
Among patients having systemic lupus erythematosus there is a percentage of 20% that have fibromyalgia syndrome as well. These patients experience increased pain in the soft tissues, tender points, and, in addition cognitive dysfunction, decreased ability to concentrate, lack of stamina and difficulty sleeping. As a treatment, we can mention anti-depressants, counseling, and physical therapy if needed.
It was discovered that medications used to treat systemic lupus erythematosus can develop symptoms like those of the central nervous system lupus. Psychosis can appear due to anti-malarials in very high doses; headache, dizziness, and in rare situations meningitis-like symptoms can be provoked by nonsteroidal anti-inflammatory drugs. Also if a patient uses corticosteroids, there can appear moods swings, psychosis, depression, agitation, confusion, if there are taken high doses can appear seizures, and anti-hypertensive medications may be associated with depression or loss of libido.
A study discovered that people that have both lupus and Sjogren's syndrome may be predisposed to develop vasculitis or cognitive dysfunction. Sometimes, circulating proteins in the blood can lead to cryoglobulinemia or hyperviscosity syndrome. Plasmapheresis or filtering the blood can ease these complications. Sometimes, pronounced decreases in platelet counts may be associated with bleeding. People with thrombotic thrombocytopenic purpura or who lack Protein S or Protein C may clot, and those with lupus, idiopathic thrombocytopenic purpura and kidney failure may bleed.
In peripheral nervous system lupus, involvement of the cranial nerves can cause visual disturbances, drooping of the eyelid(s), ringing in the ear(s), facial pain and dizziness. Symptoms of numbness or tingling in the arms or legs can appear if there is an inflammation of the blood vessels supplying the peripheral nerves. There can also appear symptoms due to other conditions than lupus and electromyogram and nerve conduction tests are usually helpful to determine if symptoms are due to some other cause. Corticosteroids are used to treat inflammation of the peripheral nerves.
It is important for your doctor to know if you experience nervous system symptoms. It is possible that these symptoms to appear due to lupus, due to a medication or a particular aspect of your life. The doctor will ask you about the symptoms you experience, he will perform a physical examination and a laboratory evaluation including a blood chemistry panel, complete blood count and urinalysis. Also, diagnostic tests like sedimentation rate, ANA, anti-DNA, anti-ribosomal P antibodies and complement may be useful in order to determine nervous system involvement.There are neurodiagnostic tests, that include CT and MRI brain scans, brain waves or electroencephalogram and spinal taps.In a few hospitals, there can also be performed PET scans.The spinal fluid may be examined for cells, protein components and antineuronal antibodies. In patients with cognitive dysfunction, neuropsychologic tests may be helpful.
The treatment for nervous system lupus depends upon its source, and can include immunosuppressants, blood thinners, antibiotics, steroids, anti-depressants, counseling or surgery. If there are evident diagnostic difficulties, a rheumatologist and/or neurologist should be involved in your care. It was seen that for many people with lupus, nervous system involvement is completely reversible.
CNS Lupus: Neurologic and psychiatric manifestations of Systemic Lupus Erythematosus
R. Swamy Venuturupalli, M.D.,F.A.C.R.
Allan L Metzger, M.D.,F.A.C.P., F.A.C.R.
What is CNS lupus?
Central nervous system (CNS) lupus refers to several different neurological and/or behavioral clinical syndromes in patients with systemic lupus erythematosus (SLE). The neuropsychiatric manifestations of lupus, which are frequent, vary from mild to severe and are often difficult to distinguish from other conditions and etiologies. Any location within the central nervous system (brain and spinal cord) may be affected with a variety of presentations from mild cognitive dysfunction to seizures, stroke or coma. Table 1 summarizes the major manifestations of CNS lupus. (adapted from "The Lupus Book"- Daniel J Wallace, M.D.)
Major manifestations of CNS lupus:
• Cognitive dysfunction (not thinking clearly, memory deficits)
• Altered mental alertness (e.g. stupor or coma)
• Aseptic meningitis (inflammation of the covering of the brain)
• Stroke (disturbance of the blood supply to different parts of the brain)
• Peripheral neuropathy (e.g. numbness, tingling, burning of the hands and feet)
• Movement disorders
• Myelitis (disruption) of the spinal cord.
• Visual alternations
• Autonomic neuropathy (e.g., flushing reaction or mottled skin)
Until recently, only those syndromes with specific neuropathology were considered to be part of the CNS lupus syndrome (for e.g., seizures, strokes, paralysis), and these conditions were thought to affect about 25% of lupus patients. In the last decade with early detection (through CT, MRI and PET scans) and improved aggressive treatment the incidence of these conditions has decreased. However, the overall incidence of CNS lupus has increased because of the recognition of conditions such as cognitive dysfunction and lupus headaches as discrete entities even though there is no specific pathology that can be found in the brain to explain these conditions. Thus, CNS lupus is now considered as being present in many patients with SLE at some point during the disease.
What causes CNS Lupus?
A variety of pathological processes may be involved in CNS lupus. The blood supply to a particular part of the brain can be disrupted due to autoimmune vasculitis (blood vessel inflammation), or clots formed as a result of antiphospholipid antibodies, or emboli that travel from a cardiac source. In some lupus patients, the thickness of their blood is increased causing hyperviscosity and this may disrupt blood flow. Anti-neuronal antibodies also may be produced in some lupus patients; these can have direct effects on the cells of the brain (neurons) and alter their function. The choroid plexus, a part of the brain that is the source of cerebrospinal fluid (CSF- a fluid bathing brain and spinal cord) may be involved thus causing diffuse problems. Several cytokines such as interleukin-1, interleukin-6 and interferon- are increased in CNS lupus and these have a direct effect on the neurons and can interfere with their function. Abnormalities of the hormones produced in the hypothalamus, pituitary and adrenal glands (the HPA axis) are common in lupus due to the disease itself as well as the effects of steroids and these abnormalities can cause some of the CNS disturbances lupus. In addition, a number of secondary factors lead to the manifestations of CNS lupus such as infection (lupus patients are more prone to certain types of infections), medications (several drugs such as corticosteroids have significant CNS toxicity), hypertension, electrolyte imbalances, uremia (renal failure), thyroid disease, atherosclerotic strokes, and subdural hematomas. The concomitant presence of fibromyalgia in lupus patients is associated with an increase in functional neurological problems such as anxiety and cognitive dysfunction.
What are the clinical manifestations of CNS lupus?
The spectrum of clinical presentations in CNS lupus is broad. The major clinical syndromes seen in CNS lupus are:
This is an inflammation of the brain's blood vessels due to lupus activity. This is the most serious syndrome associated with lupus, and is one of the two specific CNS syndromes that are part of the American College of Rheumatology's criteria for defining lupus. It usually occurs early in the course of disease (over 80% of episodes occur within the first five years of disease), being seen in about 10% of lupus patients. The typical patient presents with fevers, seizures, meningitis like stiffness of the neck, and psychotic or bizarre behavior. Brain MRI may demonstrate multiple or single areas with infarcts. A spinal tap may be needed to diagnose this condition (and exclude infection), and usually shows a high number of cells, high protein level and a high synthesis rate of immunoglobulins. Anti-neuronal antibodies may be present in the serum and/or the CSF. Usually, high dose steroids and/or cytoxan are needed to treat this syndrome.
The Antiphospholipid syndrome:
Anyone who has antiphospholipid antibodies as part of their lupus syndrome is at risk to develop blood clots, which could form in vessels supplying the brain, or travel to the brain after forming in the heart or elsewhere in the body. Blood clots to the brain (called thromboembolic events) can occur suddenly, and are usually painless. Patients may have sudden onset of paralysis, or loss of speech. Lupus does not have to be "active", for a clot to be formed. MRI and CT scans may show a blood clot. Treatment includes the usual management of a stroke, and perhaps immunosuppresant medication; but all patients who have high levels of antiphospholipid antibodies in significant amounts should be given prophylactic blood thinners (aspirin and/or coumadin) to prevent strokes and other blood clot complications.
Headaches are common in lupus patients, occurring in up to 45-50% of patients. Most investigators feel that headache as a manifestation of CNS lupus occurs as an acute presentation during a lupus flare in association with other neurologic complications. Usually abnormal laboratory tests are seen, and usually lupus headaches resolve with corticosteroid therapy as lupus disease activity improves. However, many lupus patients have headaches, which are not related to disease activity or other manifestations of lupus. Amazingly, in one well controlled study, the overall incidence of headaches, migraine and tension type were similar to the general population. Thus, there is some controversy whether there is an increase in headache incidence in lupus. Older studies reported that migraine headaches were more common in lupus patients, and the headaches were usually associated with Raynaud's phenomenon, antiphospholipid antibodies, and/or thrombotic events. However, more recent controlled studies have not confirmed these associations. Thus lupus headache as a distinct entity remains controversial and unless the headaches are associated with other neurological complications suggestive of CNS lupus, (in which case they are treated with steroids) they are usually treated symptomatically with anti-migraine medications, or anti-inflammatories such as naproxen, or ergot derivatives.
Myelitis refers to dysfunction of the spinal cord. This is a serious complication of lupus that causes paralysis or weakness and ranges from difficulty in moving one limb to paraplegia. It is caused either by inflammation (lupus vasculitis) of the sac that surrounds the spinal cord, or by clots in the arteries supplying the spinal cord (usually caused by antiphospholipid antibodies). Steroids and/or immunosuppresants are usually used to treat inflammation from vasculitis, and anticoagulants such as heparin and coumadin are usually added on. Chronic inflammatory demyelinating polyneuropathy (CIDP) and post-infectious Guillain-Barre syndrome are other conditions that can cause spinal cord dysfunction, which have a higher prevalence in SLE and may be responsive to intravenous immunoglobulin therapy.
Autonomic nervous system dysfunction:
The autonomic nervous system is that part of the nervous system which controls involuntary body functions such as regulating the heart beat, breathing, sweating etc. Although this has been poorly studied, the autonomic nervous system may function abnormally in many lupus patients. Examples of autonomic dysfunction include Raynaud's phenomenon, cognitive impairment, livedo reticularis (a mottled skin rash), and tingling and numbness of the extremities. Other causes for these symptoms usually need to be ruled out, and this syndrome is usually treated symptomatically.
Lupus patients frequently complain of confusion, profound fatigue, difficulty in articulating thoughts, and memory impairment. While blood testing confirms the presence of Lupus, other laboratory tests are usually normal. Conventional imaging and CSF examination are usually normal. A superficial mental state exam performed in a physicians office usually does not reveal any abnormalities, but more detailed neuropsychiatric testing usually reveals abnormalities in focusing, attention span, task completion, memory and decreased problem solving capabilities. A SPECT scan (a radionuclear brain scan) usually shows some abnormalities. Currently, cognitive dysfunction is thought to be caused by circulating chemicals called cytokines, and blood flow abnormalities to different parts of the brain. Cognitive dysfunction must be differentiated from depression, fibromyalgia, and behavioral alterations due to medication, infections, strokes, sleep disorders and other brain abnormalities. Usually, the symptoms of cognitive dysfunction are intermittent. Corticosteroids are have not been shown to be effective, but anti-malarials such as plaquanil and quinacrine could be helpful. Tricyclic antidepressants, or selective serotonin uptake inhibitors (prozac, zoloft, lexapro, effexor, cymbalta etc.) may be helpful, and cognitive behavioral therapy, and EEG or regular biofeedback may be very useful. Lastly, DHEA, St. John's Wort and gingko biloba are complementary medicine alternatives.
Organic Brain syndrome:
When lupus patients have a stroke or lupus vasculitis insult, these lesions may heal with scarring, which results in a permanent motor, sensory or mental deficit or even seizures. This condition resulting from a permanent damage to the CNS is known as organic brain syndrome. Its importance lays in its recognition, since there is no need to treat these lesions with immunosuppressive medicines, but they are treated symptomatically or with anti-seizure medications.
Other manifestations of CNS lupus:
Abnormalities of the peripheral nerves are seen with frequency in lupus patients. This leads to painful neuropathy with tingling and numbness of the extremities. Pharmaceutical agents used to treat lupus may affect the CNS. For example, the non-steroidal anti-inflammatory drugs such as indomethacin, tolmectin, sulindac and ibuprofen have been associated with headaches. Very high doses of anti-malarials have been associated with manic behavior and psychosis as have corticosteroids. Infections of the CNS can mimic CNS lupus. Infections such as TB, meningococcus, staphylococcus, and streptococcus are common in SLE. Lastly, opportunistic infections (they occur in patients being treated with high doses of steroids or immunosuppressive medications, by pathogens that are not normally harmful), can mimic lupus and need to be excluded when considering a diagnosis of CNS lupus.
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Is it Lupus? - The St. Thomas' Hospital "Alternative Criteria"
Dr. Graham R.V. Hughes MD FRCP
Head, Lupus Research Unit,
The Rayne Institute,
St Thomas' Hospital, London.
Source: Lupus UK News & Views, Summer 1998, Number 55. (Originally printed in Clinical and Experimental Rheumatology 1998.) This paper was presented at the XVIII ILAR Meeting, Singapore, June 1997.
Dr. Graham is one of my Lupus Specialist Heros!!
The American College of Rheumatology (ACR) criteria for the classification of lupus are, I understand, up for renewal. For over two decades they have provided for clinico-pathological surveys world-wide and have (admittedly with some rust-spots) stood the test of time.
They were always intended for classification, however, and not for diagnosis. Sadly, this worthy intent has not always been heeded and the ACR 'classification' has all too often blurred into 'diagnostic' criteria in papers, meetings, symposia and even case conferences.
To use classification criteria for anything other than just that is wrong. It is restrictive. It narrows the scope for lateral thinking in clinical medicine something which lupus, above all, allows us in abundance. Such constraints would not have allowed the birth of the antiphospholipid syndrome, for example. Yet again, some form of 'diagnostic' criteria would surely be of help. Let me give you an example.
A 26 year old woman has been diagnosed as having possible multiple sclerosis. She has suffered visual symptoms and speech disturbance. However, she has also complained of arthralgia and fatigue. Her mother, who has lupus, observed that her daughter had had a past history of growing pains as a teenager. She had read in the patients' literature that lupus can present with neurological features and wondered whether her daughter might in fact have the same disease.
Every physician reading this article will have his or her own approach to the diagnosis. The question is not academic. Does this patient have multiple sclerosis with all that this implies or a connective tissue disease, potentially treatable and reversible?
In putting my mind to this paper, I have produced an "alternative" list unashamedly for diagnosis not for classification. I have named it "The St. Thomas' Criteria" more after my own hospital than the doubting saint.
The list, comprised of ten "clinical" and four "investigative" criteria has no statistical basis. It is based solely on the experiences gained in a huge clinical practice. My epidemiological colleagues would be forgiven for demolishing these "criteria" in a full frontal meta-analysis. I know, however, they will not. They are also clinicians at the sharp edge.
1. Teenage "growing pains"
Lupus is a genetically determined disease in which hormonal influences play a role. Thus, the disease is rare before the menarche. History-taking is everything. Whilst usually diagnosed in the 20s and 30s, it is not uncommon for patients to give a history going back to their teens. "Growing pains", at least in the UK, is a label widely used for joint pains in teenage life. While usually considered "benign" or "idiopathic", it is often sufficiently severe for the child to be taken to the doctor. Some of our patients give a history of "rheumatic fever". This label still persists in the UK despite its almost total disappearance. To me, the label rings alarm bells. It is most certainly covers a spectrum of rheumatology from viral arthritis, through sero-negative arthritis to lupus.
2. Teenage migraine
Similar generalisations apply to teenage migraines. Possibly, this symptom is more clearly associated with the antiphospholipid (Hughes') syndrome. So many of our 30-plus year old patients with cerebro-vascular accidents, give a past history of recurrent abortions in their 20s and "migraine" in their teens. The classification and characterization of headache, cluster headache, and migraine is famously difficult. The symptom complex is common in the normal population. However, it is our "is it lupus?" scenario; a strong history of teenage or even adult migraine is, I believe, significant. Worth diagnostic points at least.
3. "Glandular Fever"
Prolonged teenage "glandular fever" is a label which crops up time and time again in lupus patients. Despite the interest in possible EB virus and cyto-megalovirus involvement in Sjögren's Syndrome and SLE, no cause and effect link has been substantiated. Nonetheless, in many SLE patients, prolonged periods off school due to putative "glandular fever" is a recurrent theme.
4. Severe reaction to insect bites
This, as far as I know, is not reported. yet it is a feature of so many lupus patients. Ask your patients whether they were particularly susceptible to insect bites; not only are they susceptible, but often the reactions were severe and prolonged. Whether this feature is confined to any subset (? Ro positive) of lupus patients is unknown. The skin is a major organ affected by lupus. It would be surprising if hypersensitivity to insect bites were not an important phenomenon in lupus.
5. Recurrent miscarriages
One of the cardinal features of the antiphospholipid syndrome is recurrent fetal loss probably through placental thrombosis and ischemia. In many cases, the history of repeated pregnancy loss antedates the diagnosis of the antiphospholipid syndrome (APS) by one or two decades. To be precise, this criterion is not truly a lupus criterion, but is an indicator of those lupus patients with the antiphospholipid or Hughes' Syndrome. Indeed, in our lupus pregnancy clinic we believe that if APS patients are excluded, then lupus itself is not a cause of recurrent spontaneous abortion an important point for those counselling patients.
6. Septrin (and sulphonomide) allergy
"Were you given septrin? Or sulphonomide? And did you have a bad reaction?" "Yes, doctor, disastrous. "In my clinic, we somewhat cynically refer to this as THE septrin provocation test." Almost universally positive in patients with primary Sjögren's Syndrome and usually positive in lupus, it is not uncommon for patients not only to give a history of severe rashes and other adverse reactions to septrin, but for the clinical onset of the disease to have coincided with the use of the drug.
The prevalence of central nervous system disease in lupus varies from report to report. My belief is that lupus is a primarily neurological disease in which other organs may be involved. Clearly, the careful assessment of more subtle and neuro-psychological manifestation hugely increases the number of those with 'CNS lupus'. In history taking, I have found that one of the more common features of the disease, often antedating the diagnosis by many years, is agoraphobia/claustrophobia. Obviously, there are fairly precise definitions of these clinical features, but a number of patients give clear histories. In retrospect, these features may be present at a time when the disease may well have been active. The history, varying from panic attacks in shops to fear of motorway driving, for example, is sometimes protracted, lasting months or years. In many cases, the history is not volunteered, or the episodes are considered unrelated or 'something from the past'. With modern recognition of the diversity of the CNS manifestations of lupus, it is hard not to consider such histories as "pre-lupus".
8. Finger Flexor Tendonitis
From symptoms to signs, arthralgia and tenosynovitis are common features of lupus. Although not specific, the finding of mild to moderate ten-finger flexor synovitis ("I cannot say my prayers"), is a pointer in the presence of other lupus features. It is subtly yet significantly different in pattern from, say, early rheumatoid arthritis, Lyme disease, reactive arthritis and many other causes of polyarthritis/arthralgia in a patient of this age group. Tenosynovitis without arthritis.
9. Premenstrual exacerbations
All rheumatic diseases are clinically influenced by the menstrual cycle, and none more so than lupus. Some patients are almost immobilised during the 2 to 3 days preceding menstruation. It is my practice in some cases, to alter the dose of medication during this time. Although difficult to quantify, I believe that significant pre-menstrual disease flare is sufficiently prominent in lupus to be included in this "alternative criteria" list.
10. Family history of autoimmune diseases
Does the patient have lupus? Or is it perhaps multiple sclerosis? Or, if myalgia/fatigue/arthralgia is present, is it mild sero-negative arthritis or fibromyalgia?
In old fashioned history taking, the family history is important. Lupus is genetically determined, and the presence of other autoimmune diseases in the family (including thyroid disease) is worthy of inclusion in the clinical scoring system. Indeed, as the genetics and statistics of the various autoimmune diseases become better defined, the strength or weakness of a particular family history will also become more precise. There are, of course, dangers. In our hypothetical patient, the diagnosis of lupus in the mother and her subsequent self-education could have contributed to an ascertainment bias towards a positive diagnosis. This is where clinical, as opposed to scientific, experience comes into play.
11. Dry Shirmer's test
This represents one of the most useful tests in rheumatology, and yet one of the most under-utilised. A Shirmer's test costs less than a dollar and a few minutes of time. Yet a 'bone-dry' Shirmer's test is one of the most dramatic and clear cut office tests in our armamentarium. It is often forgotten how irritant the insertion of blotting paper into the lower eyelid is. The paper is normally wet in seconds. Even elderly people and those on anti-depressants or diuretics produce tears (try it). Thus, in our patient with 'vague' or non-specific symptoms, a bone-dry Shirmer's test is worth its weight in gold. It certainly points towards one of the autoimmune diseases.
It has clinical value in a number of other rheumatological diagnostic scenarios. For example, in early sero-negative arthritis in a 25 year old (wet Shirmer's) versus early SLE, RA or SS (dry). Or at the other end of the age range, polymyalgia rheumatica (wet Shirmer's) versus late onset RA (often dry). Or tellingly perhaps in our patient an idiopathic MS (wet) or a neurological syndrome associated with lupus or Sjögren's Syndrome (often dry).
12. Borderline C4
The first ten criteria, significantly, come from history taking and examination, and the eleventh from a bedside test. The remaining three are blood tests, not anti-DNA antibodies or antiphospholipid antibodies, whose importance in diagnosis are fundamental but three tests which simply add points towards the general diagnosis of lupus in our borderline case.
Genetic complement deficiencies have been known to be associated with lupus for over three decades. Heterozygous C4 deficiency is notoriously difficult to diagnose in the absence of family testing the "normal" and "abnormal" ranges overlap widely. However, in our diagnostically "difficult" patient, especially where a family history is present, repeated "borderline-low" C4 levels would certainly represent heterozygous C4 deficiency rather than consumption. This is worth consideration in the diagnostic jigsaw.
13. Normal CRP with raised ESR
Here, in my view, is one of the most important diagnostic aids. It is 20 years since we reported the persistently low CRP (C-Reactive Protein) levels seen in SLE. CRP zero and ESR (Erythrocyte Sedimentation Rate) 100. Very few clinical situations reveal this discrepancy. The diagnostic usefulness of a very low CRP in an otherwise inflammatory situation has stood the test of time, being largely confined to lupus or Sjögren's Syndrome, and to a lesser extent, scleroderma and dermatomyositis. The rise in CRP which occurs in infection, although not absolutely reliable, is nonetheless sufficiently useful to make CRP one of the first line tests (obtainable in minutes, in theory) in a febrile lupus patient.
Cytopenias are included in the ACR classification criteria. They are also in my diagnostic criteria. For the purposes of the "diagnostically difficult" case, I have focussed on lymphopenia. In the patient with very non-specific complaints and essentially unremarkable blood tests, a borderline or low lymphocyte count is often overlooked. Common in lupus (although obviously not in any way specific), it is certainly worth including among the minor criteria.
All of us can diagnose lupus in the presence of a butterfly rash, nephritis and alopecia. the challenge comes at the other end of the spectrum. The atypical case. The mild case. The differential between real disease versus no organic disease whatsoever. The ailing teenage daughter of a known lupus patient.
In this review I have tried to highlight subtle "alternative" criteria which taken together may, I believe, be helpful in diagnosis, rather than classification.
The list is arbitrary. There is not a reference or p-value in sight. Yet I hope this paper will provide a focus point for discussion amongst those who study and treat lupus and its limitless clinical ramifications.
The "hypothetical" patient referred to at the beginning of this essay was real. She did in fact go on to develop DNA positive/antiphospholipid antibody-positive some years later.
I am grateful to my colleagues who have endlessly discussed criteria on ward rounds over the years, and to my friend Yehuda Shoenfield for encouraging me to write up this presentation for the XVIII ILAR Meeting, Singapore, June 1997.
Direct link: http://www.lupus-support.org.uk/Crit.htm