Investigations to be done for all lupus patients (both groups):

1. Complete hemogram
2. Kidney function test
3. Liver function test
4. Chest xray
5. ECG
6. Urine routine examination
7. 24 hour urine albumin or urinary albumin: creatinine ratio
8. Urine for active sediments (ie dysmorphic RBCs, RBC and WBC casts)
9. Urine RBC morphology

The last three investigations are done if urine routine examination reveals more than trace proteinuria or hematuria. The investigations are primarily indicated to identify any subclinical organ involvment.

Investigations done in life threatening cases (in addition to above):

1. dsDNA titres
2. C3 and C4 levels
3. APS panel including anti-cardiolipin Ab (IgM and IgG), Lupus anti-coagulant and beta-2 glycoprotein-1 levels (espcially if anti-phospholipid syndrome is suspected)
4. Cultures from possible infected sites (Blood, urine, sputum, pleural fluid etc) if sepsis is a possibility. Most cases of lupus patient having sudden deterioration in their clinical condition are likely to have infective etiology (as a complication of immunosuppressive treatment)
5. HRCT chest or PFT with DLCO ( in acute presentation of ILD or alveolitis)
6. Bone marrow examination, coombs test , reticulocyte count in cases of cytopenias.

TREATMENT:

A) NON LIFE THREATENING:

This basically includes SLE diagnosed on the basis of joint and muco-cutaneous complaints. The subclinical renal involvement needs to be ruled out before labeling the patient as having non-life threatening disease. Treatment of this category will include:

1. Low dose prednisolone. May be started at 0.5mg/kg and gradually tapered over 3months.
2. Hydroxychloroquine sulfate 200mg twice daily
3. Non-steroidal anti-inflammatory drugs: for temporary control of pain and inflammation on as required basis only.
4. Sunscreen application with SPF >= 30 for skin rashes and photosensitivity.
5. Mild cutaneous involvement only may be managed by low potency topical steroids by dermatologists.

Some patients with mild cytopenias or refractory synovitis and those who are unable to taper steroids may require addition of immunosuppressant like azathioprine (1-2mg/kg/day) or cyclosporin (2-3mg/kg/day in divided doses)

B) LIFE THREATENING:

This is a condition when you need to treat the patient aggressively. Usually these patients require workup and treatment simultaneously.  After confirmation of lupus as the etiology for patient’s condition (be it rapidly progressing renal failure, worsening dyspnea, mesenteric ischemia, refractory or recurrent seizures) or if these manifestations are seen in a patient previously diagnosed as lupus (may be as non life threatening initially), then aggressive immnunosuppression needs to be instituited.

Intravenous methylprednisolone 1gm daily for 3 doses is the most rapid acting drug. This however needs to be followed by cyclophosphamide or rituximab as a definitive treatment. If you cannot rule out co-existing infection then it is always safe and pragmatic to put the patient on broad spectrum antibiotic coverage according to local sensitivity pattern.

Once the condition of the patient is stabilized, they should be maintained for a long time on immunosuppressant and be monitored regularly.

COMMON PRACTICAL ERRORS SEEN IN CLINICAL PRACTICE:

I was not sure whether I should write in this heading but then I thought the whole purpose is to clean up the mistakes we are doing by sharing them amongst us. So here are few of them:

1)      Waiting for renal biopsy report before starting high dose steroids in patients with RPRF (rapidly progressive renal failure). If you have adequate evidence that the disease is lupus, eg by compatible clinical picture and positive ANA and high titres DNA, then you should not wait to document the renal histology before saving the patient. An early administration of high dose steroids can be kidney and life saving in such situations. If you wait for creatinine and patient to stabilize before a biopsy then a diagnosis may be only documented at autopsy or little less the patient may land up with shrunken kidneys and dialysis for lifetime!

2)      Starting cyclophosphamide but not methylprednisolone: This again is seen quite commonly and the logic is ‘avoiding steroids’. Wow! We better save the organ first than think of osteoporosis years later. And, it is not the high dose given for few days that matter but the long toxic doses given cause all the harm. Also, it should be remembered that intravenous cyclophosphamide takes at least 15days to act and that is enough time for the disease to destroy the kidneys. Steroids given in pulse acts within 48hours to save it!

3)      Give options: There are other treatment options that are less toxic but extremely expensive. For example, rituximab, mycophenolate mofetil etc. Patients should be allowed to make an informed rational choice and we should not force them with our decision.

Dr. Binit Vaidya MBBS, MD (AIIMS), FACR

4)      You do not need to repeat ANA titres to monitor the disease. If really needed one may use dsDNA and C3 levels to monitor impending flare or renal activity. Most of the times, clinical features and ESR/CRP are adequate for managing them.

Once these patients are stabilized, they need maintenance immunosuppression adequate to control the baseline activity. They should be frequently monitored to look for both the toxicity of medicines as well as early evidence of disease flare.

WHAT IS LUPUS?

Lupus or systemic lupus erythrematosus (SLE) is an inflammatory connective tissue disease affecting multipe organs of the body. SLE is a type of autoimmune disease characterised by widespread activation of the immune system, with Tcell-Bcell interaction, auto-antibody generation, immune complex formation and deposition and deposition.

WHAT CAUSES LUPUS?

Research is still going on studying the causation for lupus. While no definite single cause has been found, various hypothesis do exist. Studies have shown female hormones, genetic susceptibility, smoking, mutations in DNAse1 enzyme and many more factors to be associated with lupus.

HOW TO DIAGNOSE LUPUS?

Wait! Don’t jump your answer to blood tests! Lupus is a great masquerader. It can evade detection- not only from the general public but also from many busy clinicians- unless it flares to a life threatening form. Just remember the basic principle: it can affect all organ systems of the body.
So, if you find a female patient of reproductive age with complains affecting more than one organ system, thi nk of lupus as a differential. The symptoms may range from:
Fever (usually low grade), fatigue, excessive hair loss

Skin rashes: -Seen in 70%. Classical butteryfly rash (35%), discoid rash, cutaneous ulcers and vasculitic lesions. Skin problems are more when exposed to sun (photosensitivity)

Joint pains:- Seen in 90%. It can present in any pattern but the most common pattern is that of rheumatoid arthritis adding to the confusion. Joint involvement in lupus is without erosions on xray and the deformities, if present, are correctable (Jaccoud’s arthritis). And yes, the pains are inflammatory type (morning stiffness, swelling, redness, improvement with activity)

Respiratory symptoms: - dry cough and insidious onset gradually progressive dyspnea indicative of associated ILD or pleural effusion
-chest pain: pleurisy
-hemoptysis: alveolitis, diffuse alveolar hemorrhage, associated thrombocytopenia
- pulmonary infections: usually a complication of treatment but is most common pulmonary pathology in lupus-not to be forgotten!

Cardiovascular: all layers and structures you know in the heart can be affected:
pericarditis: chest pain, dyspnea
-myocarditis: palpitations, dyspnea, dizziness due to low blood pressure
-endocarditis: libbmann sacks endocarditis
-coronary artery disease: MI and angina are more frequent in patients with all connective tissue diseases including lupus.
-conduction system: heart blocks (especi ally congenital heart block in neonatal lupus!)

Renal: The most popular, though not the most common, organ involved in lupus. Affects 50% during the first year of diagnosis. Lupus affects kidneys in various severities. Exact confirmation andclassification of severity needs kidney biopsy. Patients may have features of renal failure including decreasing urine volume, dark coloured urine, edema etc. However, it is important to identify patients with early renal involvement of better outcomes. And most of those with early renal disease are asymptomatic from renal point of view.

CNS: Again, in CNS, lupus can have myriad of presentations! Seizures and psychosis are the most common ones. However, patient may present with parasthesia, weakness, hemiparesis, transverse myelitis, mononeuritis multiplex etc..

Hematological: Patients usually have cytopenias and are usually detected on routine investigation. However, they may present with excessive bleeding (thrombocytopenia), recurrent infections and fever (leukopenia) or fatigue, palpitations, exercise intolerance (anemia)

Eyes: conjuctivitis, episcleritis, scleritis, uveitis and even CRAO and CRVO related to anti-phospholipid syndrome- bascially a history of painful red eye!

The clinical features have always been confusing! And it would seem anything can be lupus! It’s the constellation of the symptoms rather than a single symptom, that guides us to the diagnosis. To make it much simple and pragmatic, the symptoms can be divided into ‘life threatening’ and ‘non-life threatening’ lupus.

Life threatening lupus:
1) CNS lupus
2) Lupus nephritis Class III and IV
3) Diffuse alveolitis or Diffuse alveolar hemorrage
4) Severe cytopenias
5) Mesentric ischemia

Non-life threatening lupus:
1) Musculoskeletal
2) Mild cytopenias
3) Cutaneous

The diagnostic workup and treatment should be fast and aggressive in cases of life-threatening lupus. However, in non-life threatening ones, a routine outpatient based treatment might suffice.

We will come in another session on approach to treatment of each of the categories of lupus patients.

Thank you.

Dr Binit Vaidya

Article By-

Dr Binit Vaidya,

MBBS, MD( AIIMS), FACR