M Yates NIHR Clinical Lecturer, Norwich Medical School, Norwich, UK

There are approximately 60,000 people in the UK with systemic lupus erythematosus (SLE)1 . Most patients with SLE are women many who are of childbearing age2. SLE is a complex multisystem disease with wide variation in disease manifestation and presentation depending on the organ system involved and typically, patients have a relapsing- remitting disease course3. The disease course is highly variable and differs from one patient to another. Due to the protean nature of SLE there are several medications used to treat the various disease states. Recommendations for the manage- ment of SLE include those from learned societies such as the British Society for Rheumatology (BSR)4 and the European League Against Rheumatism (EULAR)5 .

Fran is a 35-year-old data entry clerk who was diagnosed with lupus at the age of 26 years. Her medication includes hydroxychloroquine (200 mg once daily (od) – her weight is 65 kg), but she comes to see you increasing fatigue, myalgia and arthralgia. Examination does not reveal any signs of serositis or synovitis and her urine dip is clear. Her blood tests reveal a platelet count of 120根109/L, but no fall in her complement ratios and her erythrocyte sedimentation rate (ESR) is 17 mm/hr. You prescribe naproxen 500 mg twice daily (bd) and ask her to call you should things deteriorate or if she fails to improve.Although the evidence for the use of NSAIDs such as ibuprofen 200 to 400 mg thee times daily (tds) or naproxen 500 mg bd is of low evidence, these drugs are recommended as short courses for such problems as arthralgia and myalgia, pleurisy or fever. NSAIDs should be avoided inpatient with renal impairment.

Grace is a 29-year-old who was diagnosed with lupus 3 years ago. She takes hydroxychloroquine (200 mg daily – her weight is 82 kg), and she got married last year. She comes to see to arrange booking bloods and tells you she has stopped her hydroxychloro- quine a couple of months ago when she was planning to conceive. She has noticed a flare in her lupus rash and increasing fatigue. She wonders what she should do. You arrange bloods but realise that changes in FBC, ESR and complement may be due to preg- nancy, which you confirm with a urinary pregnancy test. She is known to be anti-double-stranded DNA antibody positive but is not anti-Ro or anti-La anti- body positive. You advise her to apply sun screen protection and ask her to restart hydroxychloro- quine at 200 mg daily and inform her hydroxychlor- oquine is compatible with conception, pregnancy and breastfeeding. You telephone her rheumatology practice nurse to let her know the news of her preg- nancy in order that appropriate secondary care follow-up can be arranged.

Despite the guidance, the use of hydroxychloro- quine in pregnancy remains low. Data from the United States found the overall proportion of women with SLE taking hydroxychloroquine increased from 12.4% in 2001 to 37.7% in 2015.6 The BSR has trait-mediated effects produced guidance on the use of anti-rheumatic drugs in pregnancy and breastfeed- ing.7 This will be discussed in more detail in the section on ‘Lupus and Pregnancy’ .David is 42-year-old supermarket supervisor who was diagnosed with lupus at the age of 34, with class II lupus nephritis. His maintenance regimen includes mycophenolate mofetil 2g daily and 7 mg of daily prednisolone. He comes to you with fati- gue, arthralgia and myalgia and wants to increase his prednisolone dose to 20mg od for a couple of weeks as that worked before. Corticosteroids have been used in lupus for decades and have been shown to be effective at con- trolling disease activity. Unfortunately, they areasso- ciated with a wide range of side effects. In addition patients diagnosed with lupus at age 20 years have a 1 in 6 chance of death by the age of 35 years most often from infection, which is largely attributed to aggres- sive immunosuppression not least secondary to high dose corticosteroids.8 The secondary care physician responsible for managing the patients care should direct judicious use of corticosteroids.
In later life there is an excess of cardiovascular disease noted amongst patients with lupus and pri- mary prevention strategies should be implemented early, such as smoking cessation, appropriate diet- ary and physical activity information provided and consideration of monitoring for hypercholesterol- aemia and diabetes risk.

Jackie is a 63-year-old retired property developer, she was diagnosed with lupus several years ago and 5 years ago was diagnosed with type II diabetes. Her drug regimen includes 20 mg of oral methotrex- ate once a week and hydroxychloroquine (200 mg daily – her weight is 92 kg). Your practice nurse carried out some urea and electrolytes (U&Es) and comes to seek your opinion. Her estimated glomer- ular filtration rate (eGFR) has steadily declined over the past couple of years 58 ml/min/1.73m2. You methotrexate and ask for a repeat set of U&Es, a urine dip and blood pressure and ask the practice nurse to contact the rheumatology team to ask what should be done with her methotrexate longer term. Although methotrexate is not licensed for use in lupus,it is used at dosages of 25mg or less per week for the treatment of arthralgia or skin rashes and can be used in combination with hydroxychloro- quine to avoid the use of glucocorticoids.4 Methotrexate is relatively contraindicated in those individuals with renal disease, particularly those with class III, IV, V or VI lupus nephritis, as the kidneys excrete the drug. Guidance on disease mod- ifying anti-rheumatic drug (DMARD) prescribing was recently updated by the BSR and recommends a 50% reduction in methotrexate dose for those with Chronic Kidney Disease (CKD) stage III, but it is contra-indicated in those with worse renal function.9

It is contraindicated in for women who are planning on becoming or are preg- nant as it is teratogenic.Karen is a 31-year-old who works in events man- agement; she JHU395 was diagnosed with lupus five years ago after presenting with fatigue, arthralgia, mouth ulcers and Raynaud’s phenomenon. Her drug regi- men includes hydroxychloroquine (200 mg od – her weight is 68 kg). She started azathioprine six weeks ago with her dosage increased two weeks ago to 200 mg od for moderate disease activity (fever, rash and alopecia with scalp inflammation) with no renal involvement. She has general malaise and you organise some blood tests which reveal normal FBC, ESR and c-reactive protein (CRP) but active transaminitis. You decide to withhold the azathioprine and contact the rheumatology team to ask what should be done longer-term. Azathioprine is the most commonly used immu- nomodulatory agent in patients with lupus.10 The dosage recommended is 2 to 2.5 mg per kg. It is compatible with pregnancy and breastfeeding and so often used in women of child-bearing age. Acute hepatitis can occur with azathioprine particularly in the first 12 weeks of starting therapy and often resolves on either withholding the medication or reducing the dose. Hepatic inflammatory activity Patients are most commonly counselled about the risk of agranulocytosis.Xiang is a 23-year-old student who was diagnosed with Class IV lupus nephritis 3 years ago. Her main- tenance therapy includes hydroxychloroquine (200 mg od – her weight is 56 kg) and MMF 2 g daily. She has been stable and achieved remission. MMF at dosages of 2 to 3 g daily has been used for both non-renal and renal presentations of active lupus and has been shown to be steroid-sparing. Monitoring of FBC, U&Es and liver function tests (LFTs) is recommended initially every 2 weeks for 6 weeks, then monthly for 3 months and at least 12 weeks thereafter.9

Nancy is a 70-year-old retired factory operative. She required rituximab last year of severe organ- threatening lupus. She is currently on maintenance therapy with azathioprine 150 mg od, hydroxy- chloroquine 200 mg od (her weight is 72 kg) and 5 mg of prednisolone. Rituximab is a chimeric anti-CD20 monoclonal antibody and caused B-cell depletion. Rituximab has been commissioned by NHS England for individuals with refractory moderate lupus and is prescribed by hospital- based physicians with expertise in managing and recording disease activity in such patients.Management of serious manifestations of organ- or life-threatening lupus should be managed in secondary care, with a period of intensive immuno- suppression to gain disease control and then a pro- longed period of less aggressive immunosuppressive maintenance therapy to prevent relapses4. Intensive immunosuppressive regimens may include the use of high dose corticosteroids in combination with either: cyclophosphamide, intravenous immunoglo- bulin(IVIG), plasmapheresis or rituximab. Sometimes drug regimens may include combin- ations or cycling of these interventions, particularly in the early or initial phases, to achieve disease control.