NSTRUCTION

Examine this patient's face (usually young women).

SALIENT FEATURES

History

• Fatiguability and tiredness (suggests anaemia).

• Joint symptoms, particularly small joints (90% of patients).

• Gangrene of the digits(vasculitis).

• Skin rash (butterfly rash on face) in sun-exposed areas, livedo reticularis,alopecia, Raynaud's phenomenon.

• Mouth ulcers.

• Hypertension, oedema (suggesting renal involvement).

• Fever, enlargement of lymph nodes.

• Bleeding from gums, excessive menstrual bleeding, purpura (due tothrombocytopenia).

• Neuropsychiatric symptoms, seizures.

• History of remissions and exacerbations.

• Drug history (hydralazine, procainamide, minocycline).

Examination

Butterfly rash - follicular plugging, scales, telangiectasia and scarring affecting thebridge of the nose and cheeks (the patient may be cushingoid due to steroids).

Proceed as follows:

• Examine the following:-Conjunctiva for anaemia (often Coombs' test positive). - Mouth ulcers (seen in one thirdof cases). - Scalp for alopecia.- Sun-exposed areas and elbows for vasculitic rash, subcutaneous nodules. -Nails forsplinter haemorrhages, nail-fold capillaries and periungual infarcts. -Hands for palmarerythema, Raynaud's phenomenon, arthritis. - Knees for vasculitic rash.-Feet for secondary oedema (secondary to nephrotic syndrome).

• Tell the examiner that you would like to examine the urine for proteinuria.Note. SLE principally affects skin, joints, kidney and serosal membranes.

DIAGNOSIS

This patient has a butterfly rash of the face with telangiectasia (lesion) due to systemiclupus erythematosus (aetiology) and has renal failure, probably due to lupus nephritis,as evidenced by the haemodialysis catheter (functional status).Read: BMJ 1995; 310: 1257-61; NEnglJMed 1994; 330: 187.

ADVANCED-LEVEL QUESTIONS

What is the histology of the skin rash in SLE?

• Liquefactive degeneration of the basal layer of the epidermis together withoedema at the dermoepidermal junction, immunofluorescence microscopy showsdeposition of immunoglobulin and complement along the dermoepidermal junction.

• Oedema of the dermis accompanied by infiltrates of perivascular mononuclearcells.

• Vasculitis with fibrinoid necrosis of the vessels.

What are the skin manifestations of SLE?

Butterfly rash, periungual erythema, nail-fold telangiectasia, alopecia, livedo reticularis,hyperpigmentation, urticaria, purpura, scarring eruption of discoid lupus.

What are the criteria for diagnosis of SLE?

Any four of the following 11 criteria are required to make a diagnosis (Arthritis Rheum1982; 25: 1271):

• Malar rash.

• Discoid rash.

• Photosensitivity.

• Oral ulcers.

• Arthritis - nonerosive arthritis.

• Serositis - pleuritis, pericarditis.

• Renal involvement - proteinuria, cellular casts (nephritis is more common inpatients with anti-native DNA).

• Neurological involvement - seizures, psychosis.

• Haematological involvement - haemolytic anaemias, leukopenia,thrombo-cytopenia.

• Antinuclear antibody - seen in over 95% of patients.

• Immunological disorder - positive LE cell, anti-DNA antibody, false-positivesyphilitic serology.

Note. American Rheumatic Association (ARA) criteria are intended to provide a degreeof diagnostic certainty, primarily for research purposes. It is often possible to bereasonably confident about a diagnosis of SLE on less strict clinical grounds. Adiagnosis of SLE is usually made when patients have three or four typicalmanifestations, such as a characteristic skin rash, thrombocytopenia, serositis ornephritis and antinuclear antibodies (Medicine 1993; 72:113). Polyarthritis anddermatitis are the most common manifestations. It should be noted that antibodies to double-stranded DNA and the so-called 'Smith antigen' (Sm) are virtually diagnostic of SLE.

What do you know about SLE in older patients?

The initial presentation of idiopathic SLE usually occurs between the first and fourthdecades of life. However, about 10% of cases may first occur in patients over 60 yearsof age. Patients with SLE after the age of 50 years less often present with malar rash,arthritis and nephritis.The diagnosis of SLE in older patients must be one of exclusion. The frequency of lowtitres on antinuclear antibody tests increases with advancing age, and a positive testmay be associated with malignant disease or chronic infection.

What do you know about drug-induced lupus erythematosus?

• Procainamide is responsible for the majority of the cases. Other causes includehydralazine, isoniazid.

• Drugs causing a lupus-like syndrome do not seem to aggravate primary SLE.

• Although multiple organs are affected, nephritis and central nervous systemfeatures are not ordinarily present.

• Antihistone antibodies are characteristic of drug-induced lupus, but are notspecific for this syndrome; anti-native DNA is almost never detected.

• Clinical manifestations and many laboratory features return to normal after theoffending drug is withdrawn.

How useful is the detection of antinuclear antibodies in the diagnosis of SLE?

The detection of antinuclear antibodies (ANAs) is a sensitive screening test for SLE.Since ANAs occur in 95% of the patients, it is hard to be certain of the diagnosis in theirabsence. The degree of positivity is diagnostically important. Serum dilutions belowwhich normal serum may be positive for these antibodies vary in different laboratories.Titres that are less than two times higher than the normal limit in any laboratory ought tobe viewed sceptically. The positive predictive value of the test increases with highertitres.

How would you manage a patient with SLE?

• Avoidance of sunlight provocation. In Britain, patients should avoid being outsidefrom l lam to 3pm from March to September and should wear protective clothing,including hats; patients should holiday in temperate latitudes or during the winter. Inaddition, sun block creams such as titanium dioxide (rather than barrier cream) areessential.

• Avoidance of drug provocation - penicillin, sulphonamides.

• Encourage the patient to join the Lupus Society.

• Educate the patient to understand that no therapy is curative and that medicaltreatment is largely empirical, selected on the basis of specific manifestations (see tablebelow).

What are the patterns of lupus nephritis?

The World Health Organization's morphological classification of lupus nephritisdescribes five patterns:

• Normal by light, electron and immunofluoroscence microscopy (rare).

• Mesangial lupus glomerulonephritis.

• Focal proliferative glomerulonephritis.

• Diffuse proliferative glomerulonephritis.

• Membranous glomerulonephritis.

Note. None of these patterns is specific for lupus.

What are the common causes of death in SLE?

The most common causes of death are renal failure and intercurrent infections, followedby diffuse central nervous system disease.R.R.A. Coombs (b. 1921), Professor of Immunology at Cambridge, is reported to havesaid 'red blood cells were primarily designed by God as tools for the immunologist andonly secondarily as carriers of haemoglobin'.Ferdinand von Hebra (1816-1880) from Vienna described an eruption that occurs'mainly on the face, on the cheeks and nose in a distribution not dissimilar to a butterfly'in 1845.Pierre Louis Alphee Cazenave (1795-1877) from Paris first used the term 'lupuserythemateux' in 1851.Sir William Osier (1849-1919) first described the systemic manifestations of systemiclupus erythematosus under the name exudative erythema between 1895 and 1904.