Fw: Is it Lupus? - The St. ' Hospital Alternative Criteria

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From: " Kathi " <pureheart@...>

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Subject: Is it Lupus? - The St. ' Hospital " Alternative Criteria "

> Is it Lupus? - The St. ' Hospital " Alternative Criteria "

>

> Dr. Graham R.V. MD FRCP Head, Lupus Research Unit, The Rayne

> Institute, St ' 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.

>

> Introduction

>

> 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 than 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. ' 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 (')

> 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

> characterisation 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

> ischaemia. 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 ' 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.

>

> 7. Agoraphobia

>

> 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.

>

> 14. Lymphopenia

>

> 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.

>

> Conclusion

>

> 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.

>

> Our patient

>

> The " hypothetical " patent 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.

>

> Acknowledgements

>

> 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.

>

> http://www.infotech.demon.co.uk/Crit.htm

>

>

>